Best unlockable items and trinkets

Obtainable by bombing tinted rocks, this item gives you a simple damage up. It's unlocked by bombing 50 rocks

Found in angel rooms and treasure rooms, Increases all of your stats up, and is unlocked by using The Bible on Mom from Depths 2

Gives you a health up and 2 soul hearts, and can be found from boss room
It's unlocked by beating 4 horsemen (famine, pestilence, war, death/conquest) and obtaining 4 cube of meat items in a single run. Horsemen are unlocked after beating Mom from Depths 2. The best way to do this is to look for "Book of revelations" item while on basement floors, since upon use it gives you a soul heart and makes a horsemen guarantee to appear in boss room (if you haven't finished it yet). This can require luck, as the horsemen on the womb floor can instead give you The pony item, making the run obsolete.

Activated 6 charge item which does the following for one room:
-Increases damage, Allows breaking obstacles by walking over them, gives a soul heart, but lowers speed. Can be found in Devil rooms. Unlocked by completing Womb 2, 3 times

This insane item replaces your tears with bombs, it's crazy as it sounds. Be careful though because bombs can hurt you. Unlocked by beating Mom's heart in Womb 2 5 times. Can be found in treasure rooms

Makes every source of damage in the game deal half of it's damage. Although it isn't really useful on floors from Basement 1 to Depths 2, it REALLY shines on Womb and future floors as on these enemies deal double damage. It's unlocked by beating mom's heart on Womb 2 7 times. Found in angel rooms and treasure rooms

Grants a familiar which every 7 to 8 rooms beaten, drops a soul heart. Helps you a lot on keeping the devil/angel room chance, but also helps a lot when you play as "???" Unlocked by beating the boss of womb 2 while playing as Magdalene. Found in angel rooms and treasure rooms

Without the doubt the best unlockable active item in the game, The D6 rerolls all items in a room into another one. It also has only charge of 3, making able to get a good item whenever you want. Isaac starts with this item after it's been unlocked by beating the boss of Womb 2 while playing as "???" If you are not playing as Isaac though you still can find it in treasure rooms

Replaces tears with a very powerful knife, which can be shot at 8 different directions, when you hold it still can damage enemies, and has a short charged attack which deals 2X of your damage and slices through enemies. Unlocked by beating Satan with Isaac. Found in Devil rooms and treasure rooms

Upon use resets the entire floor, and then disappears. Best used to get more resources and items, though you will have to sacrifice your previous activated item. Unlocked by beating Satan as "???" Found in Treasure rooms and Devil rooms

Powerful activated item which recharges within seconds, shoots a blue fire piercing through enemies and dealing heavy damage. Unlocked by beating Challenge #1 "Dark was the night", where you have curse of the darkness (no map) and have to beat Mom. Found in shops.

This trinket causes every coin you pick up have a chance to spawn a bomb pickup. If you look for secret rooms and golden chests this trinket with greatly increase your bomb count.
Unlocked by completing Challenge 3 "Large Marge", where every floor has curse of the labyrinth (XL floors) and you have to beat Mom

Alternative version of Dr. Fetus, which instead of bombs fires missiles. It's basically the most powerful passive item in the game, althought its very rarely found in secret rooms. Unlocked by beating Challenge #6 "The Doctor's Revenge!", where you start with Dr. Fetus and Doctor's remote, and have to beat Mom's heart/It lives!

Increases all of your stats up. Unlocked by beating challenge 7# "Meat 4 evar!", which requires you to beat Mom's heart/it Lives! starting with 4 level cube of meat. I recommend looking for devil rooms in this challenge

Trinket which increases damage by 2. Unlocked by beating the boss of cathedral while playing as Judas.

Trinket, which... spawns a cool lil friend which shoots piercing tears! Unlocked by beating the boss of the chest as Isaac

When starting a floor, gives you a eternal heart. Eternal hearts are rare type of hearts which, if travelling to next floor with, will turn into a permament red heart container. If you take damage which will deplete a eternal heart it will not give you a heart container. To make keeping them easier, try to get a soul heart, because taking a hit will deplete a soul heart, and you will keep the eternal heart.

The trinket itself can either help you protect the beloved devil room chance or if you have soul hearts, give you a lot of HP ups which will help a lot in tough floors like sheol or cathedral. Unlocked by beating the boss of the chest as Magdalene

Trinket which causes future devil deals to cost only one heart container. Unlocked by beating boss of the chest as Judas