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The Binding of Isaac: Rebirth is an indie roguelike video game designed by Edmund McMillen and developed and published by Nicalis. Rebirth was released for Microsoft Windows, OS X, Linux, PS4, and PlayStation Vita in November 2014, and for Xbox One, New Nintendo 3DS, and Wii U in July 2015. After an initial rejection due to its controversial content, Nicalis released Rebirth on iOS on January 11, 2017. A version for the Nintendo Switch was released on March 17, 2017. Rebirth is a remake of The Binding of Isaac, which was developed by McMillen and Florian Himsl and released in 2011 as an Adobe Flash application. This platform had limitations and led McMillen to work with Nicalis to produce Rebirth with a more-advanced game engine, which in turn enabled the substantial addition of new content and gameplay features. Two expansions have been released, Afterbirth and Afterbirth+, in October 2015 and January 2017, respectively, with more game content and gameplay modes; Afterbirth+ also added support for user-created content. A third expansion, Repentance, was announced in September 2018.

The Binding of Isaac: Rebirth (like the original) is a top-down 2D game where the player controls the character Isaac, alongside fourteen other unlockable characters, as he traverses his mother's basement, fighting off monsters and collecting items. The gameplay is presented in a roguelike style; the dungeon levels are procedurally generated through a randomly generated seed into a number of self-contained rooms, including at least one boss battle. Like most roguelike games, it has permadeath; when the chosen character dies from too much damage, the game is over. Rebirth allows a play-through to be saved at any point. Map seeds can be shared, allowing for multiple people to try the same dungeon layout.

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