Bosses spawned by It Lives will be spawned in order the first time, with Monstro being first, followed by Larry Jr., the Duke of Flies and finally Chub.
*Any normal enemy may randomly be replaced by one of its counterparts, including Kamikaze leeches, Holy leeches, bloodshot eyes, spits and Selfless Knight variants respectively.
Like in the Mom's Heart fight, getting It Lives to approximately one-third health will cause it to constantly fire red IPECAC-like bombs that leave Red Creep behind. It will spawn different enemies, starting with 4 Suckers. The easiest way to counter this is to simply hug a wall and fire tears at it, as the bombs will rarely hit Isaac directly.
Strategy for defeating It Lives is generally the same as defeating Mom's Heart, though it is advised to focus on dealing damage to It Lives whenever possible as avoiding a single boss such as Chub while fighting It Lives tends to be simpler than keeping up with the constant inflow of enemies and bosses.
Killing it for the first time unlocks the character ???, and the floor Sheol, otherwise accessed from the Devil Room. Accessing the Sheol devil room requires meeting the same criteria that spawns regular devil rooms. Killing it for the second time unlocks the immediate choice of Cathedral or Sheol upon completion, instead of the chest. Thus, you do not need a devil room spawn to get to Sheol on playthroughs 12+. If the Devil Room spawns after killing It Lives for the first time, you get the regular choice of Sheol (in the Room itself) or the Cathedral (when you come back from the Devil Room, the beam of light to the Cathedral will replace the final Chest when you leave the Devil Room), whilst further playthroughs will give you the choices side-by-side.
Eternal It lives acts exactly the same as Eternal Mom's Heart.
Defeating this boss in future runs will no longer produce the golden chest for completing this game, instead requiring you to travel to Sheol or Cathedral to win instead.
If you have enough speed, running through the beam of light that will take you to the Cathedral and going into a Devil or Angel Room (if one spawns) will not take you to the Cathedral; instead, if you leave the Devil/Angel Room, the beam of light will be gone and you will be forced to go to Sheol.
Edmund has confirmed that It Lives is in fact Isaac in his mother's womb.
This actually make some sense because It Lives's unlock text is "Your future's past awaits"
But at the same time, this is paradoxical because this would mean Isaac killed himself.
The portrait and name were added in the Wrath of the Lamb expansion. Before this the name was still Mom's Heart and the portrait was the same as Mom's Heart.
If you listen closely, you can hear Isaac's mom groaning in the background. This is the same for Mom's Heart. The only minor difference is with It Lives, you can also hear faint, kicking. This may refer to a baby 'kicking'.
Interestingly, the back from It Lives from the loading screen is the exact appearance of Mom's Heart.
It Lives is considered to be a Mom's Heart for the purposes of most achievements.