Some spawns from the Friendly Ball can cause unavoidable damage in certain rooms. Hazards or enemies can be hidden by larger allies or if many are in a group, and it will become harder to keep track of Isaac himself as there are more allies in the room. In the case of monsters that fire some sort of projectile or beam, it may be hard to discern allies shots from enemies.
The Friendly Ball works differently in this challenge, being unable to capture enemies, but summoning a random charmed enemy with each use instead. Also, as soon as a charmed friend dies, the Friendly Ball instantly recharges and can be used multiple times per room.
When a monster spawned with Friendly Ball dies, Isaac's currently equipped Active Item will be recharged. In most cases this will be Friendly Ball, but it can also apply to any other active item. This is extremely powerful when combined with Schoolbag, as it allows fast recharging of other active items.
If Isaac has The Battery, he will get two full charges instead of one when a friendly monster dies. This allows him replace or amass friendly monsters quickly in rooms with hazards or heavy enemy fire. However, one must still take care and not get too distracted by using the Friendly Ball and take unnecessary damage from enemies.
Some types of monsters are especially helpful in this challenge. Examples include:
Any monster capable of spawning other monsters in any way, as these spawned monster(s) are also friendly towards Isaac. However, friendly monsters spawned by other monsters won't count towards recharging the Friendly Ball upon death. Example: Spawning a Sack will let Isaac generate friendly spiders, but every time a spider dies it won't give him a recharge. On the other hand, if the Sack dies, he will gain a free recharge.
Mr. Mines can be summoned via Friendly Ball, but they only appear in areas with pits; if the Friendly Ball spawns nothing in a room with no pits, it must have attempted to spawn a Mr. Mine.
Be wary of hazards that can easily kill friendly monsters (e.g. Fire Places, Spikes, Troll Bombs, and explosive enemies), as they can destroy your more powerful monsters in an instant.
Since the spiked floor in a sacrifice room can hurt flying enemies, they can be used to cycle through the less useful monsters received from the ball.
However, sacrifice rooms can also be very dangerous, as monsters can kill themselves on the spikes faster than they can be replaced.
Spear of Destiny is not recommended, as it will also kill the charmed monsters spawned from the Friendly Ball.
The spear no longer kills the charmed monsters spawned from the Friendly Ball.
Using the Broken Remote trinket with the Friendly Ball charged will allow infinite teleporting.
Charmed enemies that have multiple "phases" will only recharge his Friendly Ball when their first phase is killed. For example, Lepers will only recharge his Friendly Ball when the first part of their skin detaches from them.
Be wary when using "Ace of" cards like Ace of Clubs as they will transform all of your charmed enemies into their respective pickup.
But above all else, do not solely rely on the charmed enemies to win the run; no matter how powerful the spawns are, remember that Isaac is always stronger. Do not get carried away by the large number of allies and take unnecessary damage. Good tears stats and modifiers are still important in situations where you can't use the Friendly Ball due to the lack of charges.
The title of the challenge is a play on the word Pokémon. The use of the modified Friendly Ball (and to some extent, Mom's Eyeshadow) is a reference to Pokémon Trainers battling opposing Pokémon using their Pokémon.