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Returning for its fourth season, THE 4400 explores the travails of the 4400 people who all at once returned in a ball of light to Earth; though the returnees had not aged physically, many of them reappeared with dramatic abilities ranging from enhanced reflexes to precognition. NTAC (National Threat Assessment Command) is the government agency responsible for keeping track of the returnees and investigating all things related to the 4400.

Widespread distribution of the drug Promicin has created a dangerous new world, a world in which special abilities are no longer the exclusive province of the 4400. Fifty percent of those who take the shot pay the price with their lives, while those who survive are now ostracized by a government determined to rid the world of promicin forever. But promicin distribution was only the first step, and what's next on Jordan Collier's (Billy Campbell) agenda will require an even bigger leap of faith on behalf of believers and non-believers alike.