Robert Neville (Will Smith), a brilliant scientist, is a survivor of a man-made plague that transforms humans into bloodthirsty mutants. He wanders alone through New York City, calling out for other possible survivors, and works on finding a cure for the plague using his own immune blood. Neville knows he is badly outnumbered and the odds are against him, and all the while, the infected wait for him to make a mistake that will deliver Neville into their hands.