A Nuzlocke is a fan made challenge run of a Pokémon game built on two rules: you may catch only the first wild Pokémon encountered in each area, and any Pokémon that faints is treated as dead and must be released or permanently boxed. Failing to catch the first encounter means that area gives you nothing.
The rules are self imposed; no Pokémon game has an official Nuzlocke mode. The challenge grew out of a webcomic by Nick Franco documenting a hard mode Pokémon Ruby run, and the name combines Nuzleaf, a Pokémon featured in the comic, with the character John Locke from Lost. A third rule from the comic, nicknaming every catch to build attachment, is now treated as standard by most players.
The two core rules change every decision. Your team is whatever the routes gave you, so weak and duplicate species get used seriously, and a careless turn against a Gym Leader can permanently remove the Pokémon your whole plan rested on. A white out, losing every Pokémon in the party, ends the run. Common extra rules include banning items in battle, playing on Set mode, and level caps matching the next Gym Leader's strongest Pokémon, a package often called a Hardcore Nuzlocke.
Variants handle the rough edges. The dupes clause lets you skip a first encounter if it is a species you already own, and the shiny clause lets you catch any Shiny Pokémon regardless of order. Runs end at the Champion in most games, and the run is only ever as honest as the player enforcing it.
In play"Lost my starter to a critical hit in the second gym, so that Nuzlocke is basically over."