* Sam Wheat (Patrick Swayze): A young man murdered in a mugging, who becomes a ghost. He can't physically interact with the world, but can influence it through his connection to Molly.
* Molly Jensen (Demi Moore): Sam's loving girlfriend, who is initially heartbroken by his death but learns to communicate with him through a psychic medium.
* Carl Bruner (Tony Goldwyn): Sam's best friend, who becomes suspicious of his death and eventually reveals himself to be the killer.
* Oda Mae Brown (Whoopi Goldberg): A phony psychic who unexpectedly becomes the conduit for Sam's communication with Molly. She initially doubts her abilities but eventually embraces her true gift.
* Willie Lopez (Vincent Schiavelli): A quirky artist who assists Sam and Molly. He is portrayed as a sort of "ghost-whisperer" who helps Sam navigate the spirit world.
There are also supporting characters like the police detectives investigating Sam's death and various other characters involved in the story's events.