It's the year 2012, and it's been three years since a supposed cure for cancer mutated into an airborne and physically spread contagion that nearly wiped out the entire human population on Earth. Yet, that hasn't deterred Robert Neville (WILL SMITH) from thinking he can still fix things.
A military scientist who's immune to the pathogen, Robert is the lone, non-infected human inhabitant of Manhattan, a once-thriving metropolis that's now overrun with weeds and herds of deer. Not to mention packs of infected humans, rabid beings that only come out at night to avoid physically damaging and potentially deadly contact with sunlight.
Instinctual rather than intellectual, they're beings that Robert avoids by holing up in his fortified home with his German Shepherd, Sam. Yet, he also occasionally captures some of them for testing, all in hopes of developing an antidote. Apparently that isn't sitting well with the "dark seekers" and their leader, the Alpha Male (DASH MIHOK), who's apparently evolving back into a thinking being.
As he contends with that as well as perpetual loneliness, Robert must also contend with the eventual arrival of Anna (ALICE BRAGA) and her son Ethan (CHARLIE TAHAN), apparent other survivors who make the scientist rethink his strategy and outlook on life.