Spawns a wisp that orbits Isaac and fires small spectral tears alongside him. The wisps are damaged and eventually destroyed if they make contact with an enemy, an enemy shot or an explosion.
When a wisp is destroyed, the sound of fire being extinguished plays.
A normal wisp has 2 health and spectral tears which deal 1.6-2.4 damage, and is summoned in the middle ring.
A wisp's health can be determined by its size, shrinking as its health decreases.
Multiple wisps can exist at once. Some combinations have an upper limit of 26 wisps: an inner counterclockwise ring of 6, a middle clockwise ring with 8, and an outer counterclockwise ring of 12.
The Book will combine with other activated items, possibly granting special effects on the created wisps. The recharge time will be based on the other item.
While held, guarantees the first Devil/Angel Room encountered to be an Angel Room, and increases the overall chance of getting one.
Even if a Devil Deal has been taken, Angel Rooms are still possible to encounter. If a Devil Deal is taken before encountering a Room naturally, it's no longer guaranteed to be an Angel Room and follows the usual rules.
Whenever Isaac is invulnerable the wisps are as well, but can still deal damage.
If a wisp is damaged, it will be smaller in size.
Wisps can be healed by using Book of Virtues while at maximum capacity for your current type of wisp.
While having 100% chance of Angel Room discovery, Isaac will not get teleported to a Devil Room by using some items which allow it. Instead, he will be teleported to the Angel Room, keeping his 100% chance of discovering Angel Room. This can be used to get to Angel Room on the first floor, where naturally Devil/Angel Room do not spawn, and still keep the 100% chance for the next floor.
Due to the combining effect, it is impossible to swap the Book of Virtues away normally and it acts like a passive item despite occupying the active slot.
Despite not being able to be rerolled using items, a Dice Room can be used to reroll the Book of Virtues.
This item can be used in combination with the glowing hour glass to spawn infinite wisps.
Combinations
Abyss: Spawns black-glowing red-fly wisps. Further effect unknown.
A Pony: The wisps take the appearance of "A Pony", charging ahead into enemies when attacked
The Bean: The wisps are green stink clouds residing in the outer ring, and sometimes trigger the bean's effect when destroyed.
Butter Bean: Wisp resides within the inner ring, have 1 health, do not shoot, release farts upon death, and cannot be carried between rooms.
Best Friend: Wisps are small Isaac heads with white flame. Tears have a rare chance to apply the Rotten Tomato effect, causing other enemies to attack them.
The Book of Belial: Wisps are black and red instead of white and blue. Tears look-alike to Mom's Contacts petrifying tears. Other details unknown.
Book of the Dead: The wisps are tiny skulls that fire (only cosmetic, non-splitting) bone tears. When destroyed, they spawn a friendlyBony or a Black Bony. The wisps orbit in reverse.
Book of Revelations: The wisps become tiny crosses that fire no tears within the inner ring. When a wisp dies a Harbinger familiar is spawned for the current room. Because of their lower maximum capacity, similar charge time, and inability to shoot it may be smarter to not pick up the Book when Book of Virtues is your only active item.
Book of Secrets: The wisps become tiny spinning question marks. When they are destroyed, they will reveal one special location on the level, and unlock locked doors in the current room (e.g. for item rooms, shops, and secret rooms).
Book of Shadows: Spawns a shielded wisp that isn't damaged by blocking projectiles. Additionally, since Book of Shadows makes isaac invulnerable, Wisps will not take damage whenever the shield is active.
The Book of Sin: Grants a random wisp which can occasionally drop pickups, like red hearts or troll bombs (more information needed).
The Boomerang: Any wisps created with The Boomerang will disappear when changing rooms. Tears fired up by those Wisps will fly back to Isaac after traveling the same range as Isaac's.
Box of Friends: The wisps are Black with a dark aura, and shoot dark tears.
Box of Spiders: Spawns 5-6 spider-like wisps (maxed at 12) hovering on a distant orbit. They fire small spectral tears, deals contact damage and transform into blue spiders upon destruction.
Breath of Life: When you are invincible and touch an enemy a beam of light from heaven spawns on them; if you hold the spacebar for too long you take damage and a wisp spawns.
Broken Shovel: The wisps become tiny ghosts reminiscent of The Soul. When a tear shot by the wisp hits an enemy, there's a chance for mom's dismembered leg to stomp down on said, enemy.
Brown Nugget: The wisps are brownish and do not fire with Isaac, but instead auto-fire at nearby enemies like the Nugget's fly turret. The wisps are lost after leaving the room they were created in.
Butter Bean: The wisps are white and do not shoot tears or deal contact damage, instead being consumed to reflect enemy projectiles and knockback enemies on contact. Wisps only last for the current room.
The Candle: Wisp are blue and only exist within the current room. For each activation of the candle, a new wisp is added for the duration of the blue flame. If the wisp stays after the flame disappears depends on the type of charge used to activate the blue flame: For a green charge, it only stays if the generated blue flame hit an enemy. For a blue charge, the wisp always stays. Wisps are reset to one if the blue flame does not hit an enemy.
Clear Rune: Spawns a purple-glowing rune wisp. Wisps fire normal tears and drop runes and soul stones when destroyed
Compost: Spawns dark green wisp glowing with dark purple light. Does not spawn a wisp if no pickups are consumed upon activation.
Converter: Spawns heart wisps. Note that, this is not possible while playing as Bethany.
Crooked Penny: Spawns coin wisps. Wisps have 50% chance to be doubled or destroyed.
Coupon: Spawns one green wisp that fires a triple shot of spectral tears. Some green wisps will disappear upon purchasing an item with coins.
Crack the Sky: When used for contact damage or destroyed, wisps create pillars of light.
Crystal Ball: Wisps are a crystal ball. Normal tears.
D infinity: Spawns one normal wisp and one white-glowing wisp. D infinity does not transform into any dice or reroll items.
D1: Two white six-sided dice wisps are spawned at the same time.
D4: In addition to adding random wisps, rerolls your current wisps into ones with random effects.
The D6: A white wisp and a D6 wisp are spawned, an additional D6 wisp is spawned per item rerolled.
D7: Spawns one six-sided grey die wisp. When the wisp is hit it turns blue and either applies the D7 to the current room or teleports the player to the room it was used.
D8: Spawns black-glowing dice wisps. Wisps fire normal tears. (need confirmation)
D10: The orange wisps reside within the inner ring and can reroll enemies occasionally with their shots.
D12: Wisps are blue dice. Occasionally re-roll blocks in the room with their shots.
D100: Summons a random type of wisp. Additionally summons a second random wisp if a collectible item is rerolled.
D20: All pickups in the room are destroyed. Spawns dice wisps, as well as random types of wisp (exact possible types unknown).
Dad's Key: The wisps turn into golden keys, able to open chests and doors but are destroyed in the process.
Dark Arts: Spawns a black wisp whenever an enemy is killed by Dark Arts effect.
Dead Sea Scrolls: Each wisp spawned has attributes of the active item that was triggered.
Deck of Cards: The wisps have a card-like appearance, reside within the inner ring, and spawn a card when destroyed.
Delirious: Generates a white wisp that behaves as a random type of wisp.
Diplopia: All existing wisps are doubled, and a special Diplopia wisp spawns. It is very durable and has double shots.
Doctor's Remote: Generates a wisp with a bomb-like appearance and grey aura. Wisps fire small grey tears when Isaac fires tears. When Doctor's Remote is activated, normal tears will fire from the wisps, followed by two separate rounds of larger, lighter grey tears, which explode on contact. Explosions will hurt Isaac. Tears fired from wisps surround the targeted area if close; if Isaac has more than four wisps, the tears will form a circle around the missile.
Dull Razor: Adds a grey wisp that does not fire. Possibly deals extra contact damage and has extra durability. (Confirmation required) The wisps allow you to pass through curse room doors or touch spiked rocks without losing life at the cost of 1 wisp.
Eden's Soul: Spawns a random wisp. Until the end of the run, if destroyed, a new one will spawn whenever a room is cleared.
Eternal D6: Spawns white-glowing wisps if items in the current room are rerolled. Destroy all wisps if the items are removed by the side-effect of Eternal D6.
Flush!: Generates brown wisps. Creates 1 wisp, plus 1 additional wisp for each enemy transformed into poop.
Forget Me Now: Spawns a white wisp with Isaac's head. Wisp cannot be destroyed but disappears upon going to the next floor.
Fortune Cookie: The wisps are green, and give a +0.1 luck up for each wisp.
Free Lemonade: Spawns large, yellow wisps that will spawn small puddles of yellow creep every two shots. The wisps have little health.
Glass Cannon: The wisps are white, firing larger shots. They are very easily destroyed and are all lost at the same time. If Isaac has wisps from other active items, they are not destroyed when Glass Cannon wisps are.
Error: The given collectible ("Glowing Hour Glass") does not exist.: The wisps have a tiny hourglass symbol on them, and their shots and destruction petrify enemies.
Golden Razor: The wisps are yellow and resemble coins. Their tears may inflict a Midas' Touch effect on hit.
Guppy's Head: Spawns fly wisps that are sent to the outer ring which shoot normal wisp tears inplace of the blue flies it normally spawns. Upon being destroyed wisps spawn a blue fly.
Guppy's Paw: Converts one red heart container into three wisps. The wisps have small hearts inside and a large amount of Health.
Head of Krampus: Spawns red wisps that fire red tears. Wisps cause a Head of Krampus effect when destroyed.
The Hourglass: Spawns hourglass-shaped wisps that cause a room-wide slowing effect when destroyed.
How to Jump: Spawns stationary a wisp at the location jumped from that fires in the direction of Isaac's tears. Max of 6 tears spawned this way. Wisps only last for the current room.
Isaac's Tears: Instead of firing tears in a radial pattern, 6 wisps are spawned at the same time. They are destroyed in about 3 seconds, and no more than 6 can be created this way at the same time.
IV Bag: The wisps take the appearance of a coin within the outer ring and fire blood tears.
The Jar: Consumes stored hearts to spawn heart wisps, rather than releasing heart pickups. Heart Wisps has a chance to drop a half red heart when destroyed.
Jar of Flies: Wisps will contain the summoned flies, releasing them when destroyed. Each Wisp can contain up to five Blue Flies, for a possible maximum of four Wisps. Enemies killed by wisps will not add any flies to the jar.
Jar of Wisps: The wisp amount spawned is doubled with one more added.
Kamikaze!: The wisps appear as sticks of dynamite, firing explosive shots. Although the explosions are small and weak, they can still harm Isaac if too close. The wisps also explode when destroyed.
Keeper's Box: The wisps appear as a coin, glowing in yellow. Wisps fire normal tears.
Kidney Bean: The wisps are tiny and pink and leave behind a charm cloud when destroyed.
Larynx: The wisps turn red, firing high-damage tears. Tear damage depends on the charge used when the wisps are spawned.
Lemegeton: Gives the purple wisps purple homing tears, also buffs the health of the Lemegeton wisps.
Lemon Mishap: The wisps are yellow and leave behind a yellow creep.
Magic Fingers: The wisps become coins, but fire normal tears. The wisps have a chance to drop coins when they die.
Magic Skin: The wisps are pink, but fire tears that have a chance to poison enemies.
Mama Mega!: Spawns 6 golden bomb wisps that orbit around the player. Upon being destroyed they spawn a golden troll bomb.
Meat Cleaver: Spawns 1 orbiting red wisp upon use, also cleaves each current wisp, effectively doubling them.
Mega Bean: Spawns a tiny magenta wisp with high tear height. Upon being destroyed, poisons or freezes enemies in the room.
Mega Blast: Spawns wisps that fire brimstone laser whenever Isaac use the activated item.
Metronome: Spawns a wisp based on the item that Metronome chooses. For example, if Metronome chooses Spirit Sword, the spawned wisp is a sword that fires sword projectiles. [More info needed]
Mine Crafter: Spawns one glowing green wisp that floats around the room and bounces off walls. Disappears once the room is left. The wisp explodes if hit by Isaac's attacks.
Mom's Bottle of Pills: The wisps are pills, that come in random colors. May drop a pill when destroyed. Blue fires tears that may confuse. Pink fires tears that may poison. Yellow fires tears that may petrify. Black spawns a troll bomb when holding the shot button.
Mom's Bra: The wisps glow red, and fire normal tears with a chance to fire a red, petrifying tear.
Mom's Bracelet: Normal wisps. The item is spammable, as long as there are rocks to consume.
Mom's Pad: Wisps are black with yellow fire, with chance to fear.
Mom's Shovel: Spawns 2 wisps. One wisp looks like the Forgotten's body that has more health. The other looks like the Forgotten's soul that fires normal tear.
Monster Manual: Spawns a random a wisp within the inner ring with a random tear effect (e.g. Ring Worm, Death's Touch). It appears that multiple tear effects can stack on a single wisp under unknown conditions (e.g. Death's Touch and My Reflection).
Monstro's Tooth: The wisps are teeth, which shoot teeth at a slower fire rate and higher damage.
Mr. Boom: Spawns a bomb wisp that drops a small homing bomb when destroyed.
Mr. ME!: Spawns a wisp that looks like a face in the middle ring.
Moving Box: Spawns a box wisp. Only spawns a wisp when dropping items from the box.
My Little Unicorn: Spawns one rainbow-colored wisp while active. These wisps can take more damage than normal wisps. When de-activated, the rainbow coloring slightly fades away.
Mystery Gift: Spawns one random wisp on use. After used, for the orbiting layer in which the random wisp spawned any new destroyed wisps on that layer have a chance to be replaced with a random wisp after a room is cleared up to a maximum of 8 wisps (wisps on other orbits are unaffected).
Notched Axe: Has a chance to spawn a black, silver, gold, or red wisp upon breaking a rock. The red wisps shoot lasers instead of tears. Also spawns a larger wisp with a larger radius when a poop is mined.
The Necronomicon: Spawns one black-colored wisp within the inner ring. If the wisp dies, it activates the Necronomicon effect in the room.
Pause: Spawns green wisps that temporarily freeze enemies when destroyed.
Pay To Play: Spawns one coin wisp per use, up to a maximum of 6. Coins may sometimes be dropped when a wisp is destroyed.
The Pinking Shears: Spawns a wisp in the form of Isaac's floating head. Further effects unknown.
Placebo: Spawns a white wisp that will drop a random pill when extinguished.
Plan C: Spawns 8 red wisps that deals high damage. Using Plan C will kill Isaac as expected, but wisps won't disappear if used with an item that grants an extra live.
Plum Flute: Spawns a wisp that uses Baby Plum's diagonal attack whenever the Baby Plum spawned by the flute does the same.
The Poop: The wisps resemble miniature Dips and hover far from Isaac, firing small brown tears that have a small chance to turn enemies into poop. [More info needed] Wisps spawn on the outer layer first.
Portable Slot: A different wisp is gained depending on what is won from the slot machine. Because of the varied wisp type, 20 wisps can be generated: an inner ring of 8 and an outer ring of 12. Heart wisps can take an additional hit before extinguishing. Key wisps can take the place of normal keys when colliding with objects. Instead of flies, you get fly wisps, similar to the interaction with guppy's head. [More info needed]
Potato Peeler: Spawns immortal red wisps that actively follow and damage enemies.
Prayer Card: The wisps are white, heart-shaped, hover within the inner ring, and fire Sacred Heart-esque tears.
Razor Blade: The wisps are red. Wisps fire bloody tears and have higher health.
Red Candle: The wisps are red. Wisps fire a small flame similar to the one created by Red Candle. Wisps disappear upon leaving the room.
Red Key: Spawns a red key wisp that fires red tears.
Remote Detonator: The wisps glow red, appear as bombs, spawn from detonated bombs (cluster bombs and troll bombs do not count), and fire tears that may be detonated mid-flight by re-using the active item.
Satanic Bible: The wisps are black, with a red inverted cross. Each wisp grants you a bonus chance for devil/angel room.
Scissors: The wisps are red, firing small arcing bursts of 2-3 bloody tears.
The Scooper: Spawns white-glowing eyeball wisps. Wisps fire normal tears.
Sharp Key: The wisps appear as a key in white flame, but cannot open locked chests. The wisps fire normal tears.
Sharp Straw: The wisps are red hearts, sometimes healing Isaac when destroyed. Only creates wisps when Sharp Straw generates a heart.
Smelter: The wisps are yellow and act otherwise normally. The wisps have a chance to drop a random trinket when destroyed.
Shoop da Whoop!: The wisps are white, reside within the outer ring, and act otherwise normally, but fire a smaller Shoop Da Whoop laser along with Isaac when the item is activated again.
Spider Butt: Spawns a white spider wisp that fires slowing tears.
Spin to Win: Generates up to eight wisps while charging the item, which are immediately extinguished once the charge runs out. The fire rate of the wisps is based on the speed they're rotating.
Spindown Dice: Spawns one random wisp, then rerolls all Isaac's wisps.
Sprinkler: Wisps spin as they orbit, firing tears in a fashion similar to the sprinkler itself. The firing rate of sprinkler wisps is faster than normal wisps.
Stitches: A brownish, stationary wisp is left behind when teleporting. The wisp fires in the same direction as Isaac. Wisps spawned this way do not persist through rooms.
Sulfur: Sulfur gives the wisps a red color. The wisps fire a Brimstone laser beam, similar to Azazel's brimstone, but significantly smaller.
Suplex!: Spawns 3 wisps orbiting where Isaac lands his attack.
Error: The given collectible ("Teleport") does not exist.: Spawns a blue, flashing wisp that periodically disappears, and fires tears that can teleport hit enemies somewhere else in the current room.
Tammy's Head: The pale wisps fire more rapidly, but with a very wide spread.
Tear Detonator: The wisps' tears are also detonated; the resulting tears are based on Isaac's own, rather than the wisps'. Has a chance to activate the effect when a wisp is destroyed.
Telekinesis: Tears caught by Telekinesis become wisps.
Telepathy For Dummies: Spawns a purple wisp in the middle ring that fires homing tears.
Error: The given collectible ("Teleport") does not exist.: Spawns a flashing blue wisp in the middle ring that fades in and out of existence. Enemies hit by their shots have a chance to teleport to a random location in the room.
Undefined: Spawns blue-glowing glitched wisps which fire tears with random effects.
Unicorn Stump: The wisps cycle between colors and can not be destroyed while the item effect is active. They block projectiles normally, but they do not attack - instead they provide contact damage to enemies while the Unicorn Stump is active. Summoned wisps reside within the inner ring.
Urn of Souls: One wisp spawns for every 2 seconds that the flame is active. Maximum 8 can spawn at a time. A wisp will sometimes fire a tiny blue flame instead of a tear. Wisps first spawn upon use of the item, allowing free spawning of wisps by not firing.
Vade Retro: The souls spawned from Vade Retro fire tears in the same direction as Isaac. No orbiting wisps are spawned upon use.
Ventricle Razor: Two wisps orbit the portals, one blue and one orange.
Void: Activates the-wisp effect of all absorbed items.
Analog Stick: Wisps are unable to shoot diagonally, and will shoot up or downwards instead.
Void: The Book of Virtues is considered to be a purely passive item, so only stat boosts will be gained by using Void on it. Further uses of the Void will not have the Book's effects.
In-game Footage
Bugs
Bug!
BFFS! will increase the size of wisps and obscure the screen until the game makes them invisible, but still operate as normal without any other change
Bug!
With Spin to Win, leaving a room just before the item's charge runs out causes all wisps generated by Spin to Win to remain with Isaac, and will retain their very high fire rate.
The wisps will orbit at their normal speed rather than the increased speed.
Upon entering an uncompleted boss room, all wisps from this effect are extinguished immediately.
Bug!
Using Box of Friends twice in the same room will cause the game to crash.
Bug!
When the Fortune Cookie wisp are destroyed, luck bonuses will not be removed until there is a change to Luck stat.
Abyss: Spawns black-glowing red-fly wisps. Further effect unknown.
Bug!
Spin to Win, leaving a room just before the item's charge runs out causes all wisps generated by Spin to Win to remain with Isaac, and will retain their very high fire rate.
Box of Friends twice in the same room will cause the game to crash.
Fortune Cookie wisp are destroyed, luck bonuses will not be removed until there is a change to Luck stat.
Active Item Modifiers 
Books 
Bethany Unlocks 
The Binding of Isaac: Rebirth
