The movie begins with a newspaper interview with Dr. Kripper (Emma Thompson) who is speaking about the her scientific breakthrough. She has taken the Measles virus and altered it at a genetic level so that it attacks only cancerous cells. The treatment has proven 100% effective in over 10,109 clinical trials. The film then cuts to three years later and we see that New York is deserted. Grass is breaking through the concrete, cars are rusting in the streets, and entire buildings are covered in titanic sheets of plastic with Biohazard signs plastered all over them.
Dr. Robert Neville (Will Smith) is driving down one of the overgrown streets in a Ford Mustang when a herd of deer suddenly dart out from behind a building. He guns the engine and chases them through the streets, singling one out until it leaps over a blockade with dozens of cars blocking the road. Neville screeches to a halt, looks at Sam, his German shepherd companion, and steps out with his M4 rifle to track down the deer. Silently making his way through the tall grass growing between the cars, he spots the deers tail and takes aim just as it goes around a bus and under an overpass. Cursing, Neville lowers his rifle and begins to walk around the other side,
Sam at his heel. As he approaches the corner he raises the scope to his eyes and edges around, catching sight of the deer through an abandoned car. Carefully edging his way around the car for a clear shot, Neville takes aim and A lioness leaps out from behind a car on the other side of the deer, grabbing it and wrestling it to the ground. Neville holds the rifle to his and looks as though he is going to shoot the lioness, but he lowers it as a lion and two cubs come into view. He seems torn until his watch starts beeping. Turning off the alarm, Neville glances at the sun, which is beginning to makes its way down the horizon. He turns to Sam and tells him its time to go.
Neville drives home, switching vehicles to an SUV with a large amount of gear strapped to the roof rack. As he pulls up to his house, we see several barrels, with what looks like explosive devices attached to them, scattered around the outside area of the house. As Neville exits the SUV, he grabs a satchel and a squirt bottle from the back seat. Walking backwards up to the front door, he squirts the ground and stairs behind him with the liquid inside of the bottle. A shot of the kitchen reveals it to be well-stocked and very orderly. When Neville takes a can of Tomato sauce from the cupboard, he replaces it from a stack under the table. He makes dinner for him and his dog while the TV plays a recorded news broadcast that is obviously several years old as it shows one of the hosts outside measuring the snowfall with a ruler. Neville tells Sam to eat her vegetables and not just push them around her plate. His watch alarm goes off again and he takes Sam upstairs to have a bath. After turning on his iPod player, Bob Marley starts to sing Dont Worry. He washes Sam, telling her that hell forgive her for not eating her vegetables today if she eats double tomorrow. While singing along with the music, Neville starts to zone out and looks as if he is remembering something until Sams barking brings him back to reality and the beeping of his watch. He shakes his head and then gets up and starts to cover every window with massive steel shutters and locks the door with an industrial-sized bolt. As the sun sets, he curls up in the bathtub with Sam, listening to...