Robert Neville is the last human survivor in what is left of New York City. A pandemic has left only 1% of the population alive and most of those who survived are no longer human. The infected, now lurking in the shadows, watch Neville's every move. Perhaps mankind's last, best hope, Neville is driven by the only one remaining mission: to find a way to reverse the effects of the virus using his own immune blood.

A space shuttle burns up upon reentry causing debris to land across a wide area of the United States. Tucker Kaufman, a member of the CDC, visits one of the crash sites and gets a cut on his hand. Dr. Carol Bennell begins to notice that people are starting to act strange. She turns to her best friend, Dr. Ben Driscoll. He takes a small sample of the material to Dr. Stephen Galeano and they soon learn the substance is not from Earth. Carol's son, Oliver...