Small spoiler:
Binding of Isaac is extremely hard.
It doesn't take a genius to figure that out. However, navagating your way through this harbringer of death and 'death by a million papercuts', does take a genius.

And all you have is me.

So here's an overview of what I'll explain today:
Items & You
Several Rooms of Note
Planning Ahead
Commiting Matricide
The Future & Conclusion

Let's begin.

To start off, we look at one of the most key things in keeping you alive, Items. Some give you extra health, some give you extra damage, and some make you fire an all powerful beam of death.

There are over 400 items in this game, and though some are locked until you accomplish certain things, most are given to you from the word go. These items are given to you as when you enter the treasure room for the cost of one key, when you complete bosses, or are bought from treasure rooms at the cost of 15 coins, or when they're on sale for 7 (marked by a red $ amount).

Other ways to unlock items are the following:

Cursed Rooms (spikey doors) have a small chance to give some devil room items.
Devil Rooms give items from a select pool for the cost of red heart cannisters, and spawns after you complete a boss. Taking red heart damage on a floor vastly decreases the odds of getting this room, but doesn't matter for black or blue.
Black Market: Blowing up rocks can sometimes give you with a trapdoor w/ a ladder, which give items/chests.
Angel Rooms give items for free, although are rare and chances diminish when you use black markets or devil rooms, and spend hearts (red or blue) in them. Spawns after you beat a floor boss, in place of a devil room.
Golden Chests: For one key, you have a chance to unlock a select pool of relatively weaker items, or get a couple coins, keys, and bombs.
Seven Deadly Sins Occasionally, a room will contain a mini-boss, themed around one of the catholic 7 deadly sins. They have a chance to give drop a specific item when killed.
Beggars, Arcades, etc. There are other ways to get items, but the ones above are the main ones. Beggars, Arcades, and other rooms have chances of giving items from a select pool, and thus it would take a long while to explain each one.

I think the strategy here is to just try to learn what each item does, knowing when to use keys, and determining what items you would trade hearts for and would not trade hearts for in the case of devil rooms and black markets. Angel rooms are rare, and knowing what items do is a key feature in Binding Of Isaac.

And yes, there is an item that is an all powerful beam of death. Brimstone.

As I stated in the last chapter, there are certain rooms that give items, such as treasure, devil, and shop rooms. Here are some rooms of note to pay attention to on runs:

Treasure Rooms (marked with golden door): At the cost of one key, you get an item

Shops (marked with a key hole): One key for purchasing items using coins

Cursed Rooms (marked by spiked door): At the cost of half a heart on entering, and a half a heart when you exit, cursed rooms are random and can give pills, soul hearts, devil room items, and both friendly and evil spiders.

Devil Rooms (marked by dark room after beating boss on the floor): Trade heart cannisters for powerful items, bestowing the player with flight, fear shot, and stat increases for heart containers.

Arcades (Marked with the arcade above the door): Costs a coin to enter, allows players to lose health for $, play a slot machine or a three card monte for pills, coins, bombs, or keys.

Libraries: Costs one key to enter, and contain a pool of items consisting of the game's books, space bar items that can either give hearts, or temporary buffs for that room

Dice Rooms: Costs two keys to enter, depending on which one you get, you have a chance to reroll everything. Highly discourage activating 1 or 6 pip rooms, they reroll items into usually a much worse loadout.

Binding of Isaac Rebirth has two major things that allows to the player to unlock content over a course of runs.

They are:
The Donation Machine, where you donate coins to the machine in the shop to unlock items, as well as keep the shop growing.

And Character Unlocks, where you complete a requirement to get a new character, with slightly different play style.

I will just tell you straight up what I found to be useful in this situation:

1. Unlock Azazel.

This is farely simple, as it just requires you to do three deals with the devil. Azazel is notably one of the best characters in the game, beside Isaac once he holds the D6. He has flight, starts with 3 black hearts, and has a minor beam of death. Getting him makes unlocking items a whole lot easier, as he can both fly, and can do major damage.

2. Donate like it's cursed.

Simply put, the donation machine gives both store upgrades and new items once milestones are reached. If you have spare $, give it. At least get the machine to 20 coins, so you get three items for sale instead of two, early on.

Before you ask, matricide is the act of killing one's own mother, not going into Sleepy's and stabbing the whole Certa sale with a bayonet.

Anyway, so you finally got to Mom, Depths 2, and are ready to square up against the beast that's there. Make sure you have loads of health, a decent speed, and the ability to dodge, because this boss is a pain-in-the-neck for newcomers.

Though, it is quite easy once you know what she can do.

Tips:
Avoid standing by the four doors: The boss can spawn minions or reach for you from all of them.
Watch the ground: If the shadow right below your feet starts to grow, move, lest ye be goomba stomped.
Focus on Mom: She does a lot more damage then the minions, and she has a lot more health. Goomba stomps also harm enemies.

Oh yeah, and the item 'The Bible' is an insta-kill for her.

Follow them, and you should be golden (boy).

If your reading this, conglaturations!

You've successfully beaten one of the game's many bosses, and have been awarded with even more levels, these ones even harder, and now without treasure rooms, shops, or anything that could help!

Yeah, this game has no end, really. Binding of Isaac: Rebirth is many things, but short is not one of them. Now, you have the Boss Rush, the Womb, The Cathedral, Sheol, The Chest and Dark Room to worry about! But don't worry, keep a level head, and keep on crying, because empathy is your weapon of choice.

Or Bombs.

And, on that note, I do believe I'm finished.

P.S.: This was my first guide, so please tell me how I did in the comments below!

Afterbirth brought a lot of new changes, some of which even I, the great guide creator, haven't seen yet. However, if I endeavor to be the helpful man I am, teaching all the newbies how to commit matricide (again, this means to kill one's mother, not to run into Sleepy's and stab their products), I must then endeavor to tell about the newest expansion, Binding of Isaac: Afterbirth.

Again, this guide will only cover the first three zones, that is to say, up until the 'Mom' Fight. This will not cover any Greed Unlocks, as I will go an indepth strategy guide to Greed Mode at another time. That being said, I will bring up a character introduced in the mode, Lilith.

For first time Afterbirth players, you might find yourself asking the following questions:
1. What is Greed Mode, and why am I dying a lot in it?
2. Have certain rooms changed?
3. Who's Lilith?
and finally,
4. Why is everything on fire?

I will answer #2 and #4 of those questions in this section
In the new afterbirth update, several changes were made, including like the addition of the burning basement, flooded caves, and dark depths. Each one, like the curses, can be pulled up instead of their normal counterpart. While Flooded Caves seems to do nothing but make my game lag unbareably to the point of leaving fullscreen, and Dark Depths I've never seemed to notice anything, Burning basement seems to have a key astetic. Everything is on fire.
(Maybe someone should use the water two floors below to help put it out)
What I've noticed about burning basement is the severe change in enemy types. Enemies has a 'burned' counterpart that doesn't appear anywhere else in the game (minus jumpy guy), and while there will be the occasional shooter, what I've noticed is a focus upping enemy speed and having them melee you to death. Speed is key here, as, like if your basement is on fire in real life, you should run around spraying anything you see with your tears.

Moving on, yes, rooms have changed. McMillen is now even more of an (3-letter curse) with the new alternate versions of the Treasure room. These alternate rooms range from being helpful, such as the ones with the reroll machine and the ones that give you a choice of two items (bombs are incredibly helpful for both), to the neutral (summon three harmless flies, only two fires), to the downright BS, (Looking at you, one that requires me to walk on spikes).

Other than that, there is also the closet, which are half the size of normal rooms, and can involve anything from treasure rooms, Devil rooms, and Boss rooms because again, McMillen is a sadistic genius.

(Please don't rage at me in the comments for previous statement. See Lost for more info.)

A note of warning, I have no clue what items are in the base spawn pool for Afterbirth. I would look them up, but my time is very limited, and I have to go watch some more NorthernLion. Suffice to say, when I booted up Afterbirth, it thought I was so good that it decided to give me about half of the achievements straight off the bat.

Edmund McMillen is nothing if not a benevolent overlord. With one hand, he takes, but with the other, he gives. Then he claps both of them together and makes thunder fall upon ones head. Afterbirth added a whole lot more synergies that make basic items now a lot more useful, while changing some. Here's the short list of stuff I found to be most important:
1. 20/20, Quadshot, and Third eye now synergize, creating what I would like to call 'the shotty'. New Challenge Please.
2. Brimstone and Technology, when one death laser isn't enough.
3. Three Dollar Bill now cycles every 3 seconds (for the dreaded Polyphemus Soymilk disaster)

The Afterbirth Update might give you the want to try out new items to see if they are better. The following aren't:
Soy Milk, The Bean, Cursed Eye, Bob's Brain, Anarchist's Cookbook, Anything with the word 'Bean' in the name, and also the Lemon.

Afterbirth has also introduced several items of note:
1. Sack Head (looks like a bag)
Greatly increases chances of finding sacks, as well as replacing previous items on floor with sacks. Basically it's like half a normal chest, with three times the spawn rate. Quantity over quality.
2. Restock (Reduce, reuse, restock)
Shops never run out of items, so it's essentially a way to max out on blue hearts if you got the $$.
3. Car Battery
Doubles Space Bar Items. This is insanely overpowered when used in conjunction with any one room item that is not the bean.

Of course, all of these are shop items. Greed mode makes shops better now, as they should be.

To all those who've read this far, thank you for doing so. Afterbirth is an expansion I love, and I hope to beat it one day, but I know that I will spend an eternity in the depths when challenging a certain boss with a certain character that I will not say because of spoilers, but that speedr un is going to be a pain in the neck.

I may later post a guide on beating certain bosses, if so, I'll put a link below:

And my guide on Greed Mode's workings:


Anyway, see you in Sheol, you matricidal maniacs.