Essential Unlockables - The Complete Guide (The Binding of Isaac: Afterbirth+)

Disclaimer: This video was made during the Afterbirth+ era, but all of these items are still very powerful and worth unlocking in Repentance. There are some minor differences in unlock methods and what certain items do, listed below.

- Restarting 7 times in a row now unlocks Scared Hearts instead of Half Soul Hearts, which are instead unlocked by defeating Mom's Heart 5 times
- The unlock requirements for Challenge #4 : Darkness Falls have been updated - you now also need to unlock Sacrificial Dagger by beating The Chest with Eve
- Challenges 4, 11 and 19 seem to be bugged and will randomly refuse to be unlocked
- Blank Card now only works with cards, not runes
- Deep Pockets now lets you hold a maximum of 999 pennies instead of its previous effect
(let me know about other differences I'm missing in the comments!)

Sections:
0:00 - Intro

1:09 - Azazel

2:44 - Eden
3:16 - Mom's Knife
4:09 - Blank Card
5:33 - The D6
6:48 - The Polaroid
7:42 - D20
9:19 - Bloody Penny
10:19 - Counterfeit Penny
11:35 - Swallowed Penny
13:30 - Jera
14:43 - Algiz
16:29 - Perthro
17:36 - Ansuz
18:21 - Dagaz
19:34 - Chaos Card
21:04 - Death's Touch
22:10 - Epic Fetus
26:08 - Outro

This video has been an insanely long time in the making (at least by my standards, since it took 3-4x longer than my previous guide), and I felt really tired after finally finishing it, so I won't start work on any new guide for at least a few weeks so that I don't burn out.

That said, if there is demand (especially around the Repentance release period), new guides will almost certainly come out.

Special thanks to Adrian Nuñez, who gave me the idea for this guide as well as a lot of encouraging words. Sorry for the 3-month wait, Adrian!

As before, feedback and constructive criticism is appreciated, and I'd love to hear what guides you think I should make next.

Sources:

REEEEEE Sound Effect

THAT Crowd Gasp

[Spoiler] reward for a [Spoiler] achievements isn't actually bad like some people assume (details in comments)

Drum Roll - Gaming Sound Effect (HD)

Footage and editing by yours truly, images mostly from the Wiki (and some Twitch emotes)

[NamiZu]

Why is this video not more popuar? This is really helpful and the video is well made, quality content

[barelycommentary]

Man, I found this video completely by mistake but it was exactly what I needed to hear, my issac runs are about to get so much better, thanks for sharing man!

[RektorMcGitgud]

For anyone who owns Repentance, be aware that the unlock requirements for Challenge #4 : Darkness Falls have been updated; you now also need to unlock Sacrificial Dagger by beating The Chest with Eve.

[umcaraaleatorioeggs]

"The Family Man"
Hey Louis, remember when I was in The Binding of Isaac?

[percyvile]

Would like to see an update to this for repentance

[Kellestial]

This video was super helpful, you explained everything like you would to a complete beginner and not assuming any prior knowledge. Wish there was more videos explaining stuff in this way since it would allow more players to get into the game. Time stamps in the desc are also nice

[muhammadarif]

Just bought afterbirth+ in 2023, and i found this game way too good. I love the guide you've done aswell. Very easy to understand and straight forward. Never knew there was so much to discover in isaac.

[Justdifferent]

This video is great! I just got Binding again for the first time in a couple years and i’m starting all over, so this is super helpful for getting good items so i can be on my way to crazy runs again. 🙏

[rafaelpena]

Wow I can't believe this video has less than 5000 views. This was such a great guide, and well edited too. Keep it up!

[manuelvallet]

I hope this video will help a lot of people

[vvzxccvv]

lost my progress and started a fresh save after a long break and I've been looking for a guide like this to help me remember all of this, thank you so much

[mrworsethanall]

"With the downside of never being able to pick up red hearts..."

**proceeds to show the polaroid**
Lol

[bilt]

This video is the help we never got from other isaac content creators. Nice job and it was very helpful.

[cherryfuchs]

Jesus, that video is incredible! I can only imagine how long it took to produce. You went all the way for most of it, just to show it on video. Very nice! Thank you

[publiovirgilio]

Bro this videos is amazing. I can't just imagine the amount of work surrounding it. This is literally one of the best informative videos in youtube about this game and has less than 2k views!!! And most importantly, it is very entertaining. I already have all items in the game but i watches the whole thing. 👍

[TheMatzestar]

This video deserves more attention. Very good guide.

[WaterBisquitte]

Bro dropped this, hit a milli then disappeared

[The_Deep_Blue]

a more update for repentance: in repentance theres now the alt path, which is unlocked by beating hush 3 times, and you can access it by beating mom's heart 10 times and reaching hush in 30 minutes or less
some good characters to beat hush with are:
magdelene: unlocks purity, giving a massive tears, damage, speed, or range up until you get hit, and it shuffles into a new one
eve: unlocks athame, giving enemies a fairly high chance of spawning a black brimstone-esque ring when they die, making it one of the best room clearing items in the game
azazel: unlocks maw of the void, remember those black rings spawned by athame? its basically that but on command on a fixed charge timer
eden: eden's blessing, a tears up and a random item on your next run, making your next start a bit easier
lilith, whos unlocked by beating greed mode as azazel: probably the best to unlock out of all of these, giving you a familiar that shoots your exact tears at 75% damage, making it technically 20/20 with a bit higher dps, however its harder to aim with the incubus than 20/20 so it balances out overall

you might wanna also unlock bethany at this point, as she has some really good unlocks, she can be unlocked by beating mom's heart on hard mode without losing a life as lazarus
when you unlock bethany id also suggest taking a detour and beat isaac and ??? as her to unlock book of virtues, basically giving your active items an upgrade, and blessed penny which makes it so pennies have a chance of dropping half soul hearts, which are both incredibly potent items

after unlocking the alt path, here are some good characters to beat mother with
bethany: unlocks revelation, basically the holy variant of maw of the void which has lower dps in exchange for 2 soul hearts and flight, and a straight beam rather than a circle
if you unlock him, keeper: you probably wont have him for a while now but this unlocks keeper's sack, basically making it so buying items gives you some damage, range and speed
cain: unlocks guppy's eye, giving you another guppy piece to find alongside having the benefit of seeing whats in chests, sacks, and other miscellaneous things which drop items like fires and keeper statues
eden: unlocks 'M, which is a trinket which rerolls your active item whenever you use it, this sounds bad on paper but when you realise you can drop a trinket this becomes super broken, basically letting you get any super powerful active item if you use it enough

after beating mother, you'll unlock jacob and esau, one of the hardest characters in the game, but also has some of the most powerful unlocks in the game, like rock bottom, the stairway, birthright, damocles, and genesis
you'll also unlock seeing double and isaac's awakening, seeing double unlocking an ok trinket, while isaac's awakening unlocks spirit sword, giving a really powerful item, however its not too synergistic and it'll end up giving you hand cramps probably

you'll also unlock a mysterious door which can be openned by using the polaroid or negative on it, which is where i'll end this, you'll have to explore that for yourself

[chefboypablo]

This guide made the game much better THANK YOU!

[Ablaire]

I literally just got back into playing this a few hours ago, after about 2 years… YouTube recommendations could not have delivered in a more perfect time.