- Duplicates your current Familiars for the duration of the current room.
- If Isaac has no familiars, a Demon Baby will spawn for the duration of the room.
- 1UP/Dead Cat - Familiars are duplicated but lives are not added.
- Best Bud - The fly will circle Isaac if used before taking damage. However, the fly cannot be duplicated.
- Bob's Brain - Adds a another brain. When used upon entering a room, Isaac can launch the brains immediately.
- Car Battery - Adds two copies of each familiar.
- Cube of Meat/Ball of Bandages: Upgrades the familiar for the current room.
- Daddy Longlegs - Copies the familiar.
- Guillotine - Duplicates the head orbiting Isaac's body, but only one head will shoot tears.
- Incubus - All Incubi retain tear-changing effects and stats.
- Isaac's Heart/Isaac's Head/???'s Soul - These familiars are not copied.
- Key Piece 1/Key Piece 2 - Copies the key parts but will not complete it.
- Pickup generating familiars - All familiars, original and copied, will drop pickups independently.
- Smart Fly - Each time used will add an attacking fly.