Cubes of Meat from Potato Peeler cannot be duplicated or upgraded.
Blood Puppy: Tames an angry Blood Puppy and spawns another temporary one.
Bob's Brain: When used upon entering a room, Box of Friends eliminates the item delay, which allows Isaac to launch Bob's Brain immediately.
Book of Virtues: Spawns black wisps on the middle ring. After creating a wisp, Box of Friends also gives temporary copies of all of Isaac's wisps, including any extra copies Box of Friends made.
Incubus: Creates additional Incubus familiars, which share the same tear modifiers as the player.
Lil Dumpy: Will copy Lil Dumpy, adding an extra charge to Lil Dumpy's Holy Mantle-like protection.
This process can be repeated to make Isaac near-invincible.
Smart Fly: Very useful on Greed mode, as using it will add an attacking fly, killing enemies and bosses very quickly.
Twisted Pair: Creates additional Twisted Pairs with the same tear modifiers as the player. Multiple twisted pairs will line up horizontally, covering a broader area.
Abyss: Flies gained from Abyss do not count as familiars for Box of Friends, and are not copied.
Best Bud: If used before taking damage, the white fly will circle Isaac. However, multiple white flies cannot be spawned, so using Box of Friends after taking damage or using it multiple times in a room creates no effect.
Buddy in a Box: Creates another randomly generated familiar, rather than copying the same one.
Bumbo: Will spawn a level 1 Bumbo regardless of the original Bumbo's current level.
Tinytoma: Сreates an orbital even if it is destroyed. If the copy splits into smaller versions, they will remain when moving between rooms.
Guillotine: Duplicates the Head circling Isaac's body. Only one head will shoot tears.
Considers the second head as an extra copy, granting Isaac a temporary stat boost for the room
Hallowed Ground: All poop familiars turn into white poop at the same time, and their effects are accumulative. A new poop familiar appears even if the previous poops have been used up.
Isaac's Heart / Super Bum: Not copied. They will not spawn a Demon Baby if no other valid familiars are found, unlike other familiars that aren't copied.
Key Piece 1 / Key Piece 2: Key pieces are multiplied, but do not complete the other half.
Milk!: The familiar itself doesn't appear, but instead, it decreases tear delay by 2 (effective tears up) when used, without needing to take damage.
No extra tear delay is granted, neither before or after breaking.
Monster Manual: Familiars spawned by Monster Manual are not copied. It will still spawn a Demon Baby if a familiar from Monster Manual is generated and there are no other valid familiars that can be duplicated.
Multidimensional Baby: Each copy of Multidimensional Baby follows the previous copy with a 2-second ( 0.66-second) delay. Tears shot through multiple babies will only be duplicated once.
Quints: Existing Quints familiars will not be duplicated, nor more will be created. If Isaac has no other familiars, the generated Demon Baby will hover with the Quints instead of following Isaac.
Shade: A new follower Shade spawns even if Isaac has already absorbed the original.
Demon Baby will spawn for the duration of the current room.
Familiar Modifiers 
Lilith Unlocks 
Ultra Greed Unlocks 
The Binding of Isaac: Rebirth
