Roberta is a bored suburban housewife who is fascinated with a woman, Susan, she only knows about by reading messages to and from her in the personals section of the newspaper. This fascination reaches a peak when an ad with the headline "Desperately Seeking Susan" proposes a rendezvous. Roberta goes too, and in a series of events involving amnesia and mistaken identity, steps into Susan's life.

Having both lost their jobs, two strangers become unlikely friends after a run in with a would be robber, who is actually a hitman with a grudge against the two.