Can men and women be friends and not have sexual feelings towards each other? Harry (Billy Crystal) and Sally (Meg Ryan) meet in college and share a ride across country and discuss just these points. There lives end up crossing many times after that and they remain good friends. Each time they seem close to taking the next steps, one or the other doesn't think it is the right time and they back away. Where is Mr. Right? Is there really such a thing as Mrs. Right? They both are searching for the one thing they might find in each other but must decide if it is worth it to risk their friendship for a chance at true happiness. Everything in life is pushing them together, but will their fears get in the way?