If Isaac has any Familiars, The Siren sings, charming up to 3 familiars at a time to assist her and turning their effects against Isaac.
Isaac's Familiars when charmed retain most of their behaviors when assisting The Siren but can now deal contact damage and block shots.
Charmed Familiars have 60 HP and returned to Isaac when killed.
If she has less than 3 charmed shooting Familiars from Isaac, she summons up to orbiting 3 Siren Minions of her own. These Familiars behave identically to Brother Bobby but with a slower fire rate and can also be killed. She then glides around the room for a few seconds, letting her familiars use their effects against Isaac. If she has any familiars alive after this, she swipes at Isaac, launching all remaining familiars in a cluster in his direction.
When the cluster collides with a wall it kills all the Familiars and releases a burst of radial projectiles and a cluster of disorganized projectiles.
The amount of projectiles launched during this attack depends on the number of familiars that collided with the wall.
Swipes a short distance in Isaac's direction, releasing 5 projectiles.
Sinks into the floor becoming invulnerable and chases Isaac, leaving a trail of slowing Black Creep. After reappearing, she swipes at Isaac, shooting a spread of 5 projectiles.
Screams, emitting a consistent shockwave around her and spawning 9 pulsating rings of projectiles that expand slowly outwards. These projectiles split into two when far enough.
This attack pushes Isaac away like an inverted Gaping Maw.
The rings of projectiles have openings towards Isaac's general direction that disappear as the projectiles split.
Upon death, The Siren burns away, leaving behind her skull.
The Siren in-game.
The Siren's skull.
Bombing the skull that the Siren leaves behind spawns and unlocks the Forgotten Lullaby.
Bombing the skull in subsequent runs treats it as a regular Skull in regards to its drops.
Leaving and returning to the room causes the skull to disappear.
The Siren can charm Lilith's Familiars, including her Incubus, hence making Lilith a difficult character to kill The Siren with. To counter this, either bait The Siren into launching the familiars into the wall and killing them or use bombs/active items to deal damage.
Charmed familiars with a charged attack (eg: Lil Brimstone) hold their charge until the Siren launches the familiars.
Charmed familiars that are thrown (eg: Bob's Brain) do not count towards the count of 3 familiars that orbit the Siren but are included in the cluster thrown at the end of the attack.
If the Siren has charmed the 1up! or Dead Cat familiars and dies, she will use one of their extra lives to revive herself at respectively full health or 10% of her health.
Charmed Tinytoma orbits The Siren but still blocks hostile projectiles and turns into friendly Blue Spiders after being destroyed. It will also not return to Isaac when destroyed and will spawn charmed again for The Siren.