Will Smith
The protagonist and presumed to be last or at least one of the last few non-infected humans living on Earth after a global pandemic hits and decimates a large percentage of the human race. The audience vicariously experiences the immense isolation Dr. Neville is subjected to because of the pandemic. Tries his best to keep a semblance of his former life by setting up mannequins strategically placed in various areas in the city to create the illusion of active, bustling city life. He carries out make believe conversations with these mannequins, going as far as to give them names and background stories in an attempt to keep sane. He trains constantly because he is in perpetual danger from the infected humans who have changed into vicious, vampiric creatures. Dr. Neville also makes daily incursions into city in order to scavenge for parts he needs to keep his generators running, ammo, food, and most importantly living samples he needs to formulate a vaccine against the virus. He is driven primarily by his desire to cure the disease that ravaged humanity.
Salli Richardson-Whitfield
Dr. Neville’s wife and mother to their only child, she appears on screen during flashbacks. She is seen holding their daughter as they are ushered into an underground bunker. It is implied in the film that they do not survive despite having been moved into a supposed safe area.
Willow Smith
Dr. Neville’s only child, she, like her mother, appears on screen only during flashbacks. She is a young child of about 3 or 4 when they are moved into an underground bunker as her father works on a cure for the virus.
Sam
Sam, or Samantha is Robert's German Shepherd and his last remaining connection to his family and ultimately his humanity. She is injured while defending Dr. Neville against two infected humans that caught him off guard. Unlike him however, Sam doesn't have his natural immunity against the virus. She contracts the disease and begins to slowly mutate. She is put down by Dr. Neville before her transfotmation is completed.
Alice Braga
Another a survivor of the virus that has decimated practically the entire human race, she comes as a great surprise to Dr. Neville who has all but given up hope on his situation. She arrives with a young boy, Ethan, in tow. Their arrival is truly providential, as Dr. Neville has become reckless, blinded by rage as he rushes out to fight swarms of the infected humans. He has all but lost his will to live by the time she makes her appearance. She reports that there are isolated pockets of survivors living in the northern climates because the virus unable to withstand the cold. This news reinvigorates Dr. Neville and pushes him to continue working on the cure.
Charlie Tahan
Ethan is a young boy traveling with Anna, a survivor like herself. He seems to be largely unaware of how dangerous the world has become after the global pandemic. He, like most kids enjoy watching cartoons. Dr. Neville is generally uncomfortable around Ethan, perhaps because he is reminded of his daughter who was around the same age he was when he saw her last.
Dash Mihok
Dash plays the Alpha Male of the infected humans. He appears on screen as a motion capture, digitally modified render of an infected human. Infected humans mutate into hairless, pale-skinned humanoids, beyond the aesthetic changes though they also undergo massive psychological and physiological changes. They become stronger, more agile, they hyperventilate because of an increased need for oxygen but their minds devolve into a primal state, turning them into creatures that can only feed on blood, making them truly dangerous. Worst of all, like the storybook vampires, they spread the infection through the wounds they cause. The Alpha Male though displays a greater regard for his own kind than others and is even prompted to venture out into the sunlight in his attempt to rescue his mate, despite the danger to himself.
Joanna Numata
Joanna plays the Alpha Female of the infected humans. She appears on screen as a motion capture, digitally modified render of an infected human clad in ragged cut-off shorts and a tank top shirt tied in a knot. As part of his ongoing research in looking for a cure, Dr. Neville regularly goes out on “hunts” where he subdues and gathers samples of infected animals and humans. In one of his forays he manages to unwittingly capture the Alpha Female of the infected humans, which prompts the infected humans to go on the offensive with Dr. Neville.
