Basada en la novela de Richard Matheson. Año 2012. Robert Neville (Will Smith) es el último hombre viviente en la Tierra, aunque no está solo. Los otros hombres, mujeres y niños se han convertido en vampiros, y están todos sedientos de la sangre de Neville. Durante el día es el cazador, buscando a los muertos vivientes mientras duermen, pero en la noche debe esconderse esperando el amanecer...

Robert Neville is a scientist who was unable to stop the spread of the terrible virus that was incurable and man-made. Immune, Neville is now the last human survivor in what is left of New York City and perhaps the world. For three years, Neville has faithfully sent out daily radio messages, desperate to find any other survivors who might be out there. But he is not alone. Mutant victims of the plague -- The Infected -- lurk in the shadows... watching Neville's every move... waiting for him to make a fatal mistake. Perhaps mankind's last, best hope, Neville is driven by only one remaining mission: to find a way to reverse the effects of the virus using his own immune blood. But he knows he is outnumbered... and quickly running out of time.