Once the boss of a floor is killed, the dead player is reborn with all the items they once had, but with half a heart. If a player dies, they become a ghost baby that can only deal minimal damage and press buttons.

If you start a normal game and player 2/3/4 presses Start while in the starting room, a mini character selection wheel displays at the top of the screen, with which that player can choose any unlocked character, or a random character. Dying as one of the available special babies will remove it from the pool. Joining as a co-op baby will bring up a menu that allows the player to pick from 5 special babies. Babies always have flight, but they cannot interact with objects like items and pickups, except for certain special babies like Magnet Baby and Isaac 2. Subsequent pressing of the join button will despawn the baby, giving Isaac the Red Heart container back.Р”В«abies share Isaac's stats except for health and damage babies deal half of Isaac's damage. (These versions can also support up to 4 players.)Р”В¬o-op players can join in at any time as a random baby, taking a Red Heart container away from Isaac and giving it to the second player. The PlayStation 4 and Steam versions of the game are capable of both local and online multiplayer via PS4's 'Share Play' and Steam's 'Remote Play Together' features. The Afterbirth DLC increased this to 4 player local co-op. Rebirth features 2 player local co-op on PC. For items that follow Isaac, see familiar.

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