In Matheson's novel (set in the late 1970s), a world-wide plague has wiped out most of mankind, while those who have survived have become literally blood-thirsty vampires. The one remaining human, Robert Neville, finds himself having to barricade his home at night when the vampires try to capture him for his blood. Neville spends his days hunting down the creatures (who sleep during the day) and staking them. The monotony of this day-to-day existance depresses Neville, but eventually he snaps out and, using what's left of his local library, does research on the plague in order to find a cure. Then one day, he discovers he may not be the only human left...
After England's Hammer Films briefly tried to adapt the novel from a screenplay by Matheson, only to run into censorship problems, the story finally came to the screen in 1964. Titled The Last Man on Earth, it was an Italian/American co-production (filmed in Italy in black & white) directed by both Sidney Salkow and Ubaldo Ragona, and starred Vincent Price as Neville (here called Morgan). Although given a nice restoration on DVD from MGM a few years back (and available from us here), it's fallen into the public domain. You can access it online here. Though Matheson's basic screenplay was retained, the author didn't like the changes that had been done to his work and his onscreen credit reads as "Logan Swanson".
In 1971, star Charlton Heston and director Boris Sagal, with a screenplay by John William and Joyce Hooper Carrington, produced an American semi-remake (filmed in Los Angeles) entitled The Omega Man. Here, Heston's Neville (not Morgan) is set upon by albino mutants (!) who want to make him... one of them. (Nope, none of this wanting to drink his blood stuff.) For a full summary of the film and the alterations they made to the original story, read this entry from Wikipedia.
In between these two versions, Pittsburgh's own George A. Romero directed and co-wrote an unacknowledged remake, 1968's Night of the Living Dead. This drive-in/grindhouse cult classic, which substituted zombies for the book's vampires, spawned a seemingly inexhaustible number of sequels (including a 1990 remake), many by Romero himself, plus remakes of the sequels and countless imitations, especially in Europe, of which 2003's sublime 28 Days Later (and it's somewhat disappointing sequel, 2007's 28 Weeks Later) is the most recent. It's beyond the scope of this post to detail each of these films, but I can at least acknowledge their existance and importance in relation to Matheson's original work.
Finally, after years of pre-production delays (at one point Arnold Schwarzenegger and director Paul Verhoeven were attached to it), star Will Smith and director Francis Lawrence released their version of I Am Legend (again, without vampires and with an ending very different from the book's) to box office success in 2007. A prequel to the film has already been announced in the movie trades. Hard to believe a novel written fifty-five years ago (and available from the library; go here) still has this much life in it!