Effects: This curse is only applied after taking damage from a mini-boss, and may stack with existing curses. The possible effects are determined by the damage source:

• Asmodeus - Enemies cannot be Charmed (excluding those spawned by Isaac)

• Beelzebub - When entering a room with one or more items in it, Isaac must take at least one within ten seconds or they will disappear and Isaac receives half a heart of damage. If the room is left without taking an item, Isaac will receive a half heart of damage.

• Belphegor - Reduces the chance of receiving an Angel or Devil room at the end of the floor, equivalent to having taken red heart damage.

• Leviathan - Isaac takes half a heart of damage when using a pocket item, such as a card or pill.

• Lucifer - Isaac takes damage when picking up an item for the first time on the floor.

• Mammon - Isaac takes damage when picking up coins or otherwise gaining money; this is equal to half a heart per five coins.

• Satanus - Isaac takes damage when placing a bomb.

Effects: Prevents Flight for the floor, regardless of its source

Effects: This curse is applied as part of an optional difficulty mode, and replaces all current and future curses. The possible effects are determined by the severity of the curse:

• Enemies gain health regeneration

• Chance to remove a pip of charge from Isaac's active item when taking damage

• Has a small chance to increase damage taken by half a heart

• Core pick-ups are replaced with their standard variants, but have a small chance to be removed entirely

• When entering a new room, has a small chance to remove all special tear effects from Isaac (such as Homing)

• When entering a room with enemies, has a chance to convert one or more into a random champion variant; these enemies also become immune to status effects (such as Poison)

Effects: Reduces one of Isaac's six major stats. This penalty may be removed by exploring at least half of the total rooms available on the floor.

Effects: This curse is only applied after dying and reviving, and may stack with existing curses. It significantly reduces both Luck and Move Speed for the remainder of the floor.

Effects: Increases Isaac's sprite size (and hitbox) for the floor

Effects: Replaces all chests with Mimics, and blocks all passive items that affect chest value, spawn chance, rewards, or like effects while on the floor.