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The series follows the survivors of Oceanic flight 815, which crashes in an unidentified island in the Pacific Ocean. The group of strangers must learn to cooperate in order to survive the island's challenges, which are vastly more complicated than initially thought. Despite the standard "desert island" scenario almost none of the plot revolves around survival; the core storyline is built around a global conspiracy involving a mysterious doomsday machine and a scientific project built on the island, as well as supernatural events including [[ghosts]].

Episodes typically center around one character, with events on the island mixed with flashbacks to important parts of that person's life before the crashor flash-forwards to events years later. These scenes take place between 1961 and 2008.

Like [[24]], the show has been criticized for its depiction of torture as a useful interrogation method. One of the series' main characters is a former Republican Guard torture expert.