Andy Richter Controls the Universe

• Andy Richter: The character, sharing his name with the actor, is an aspiring writer living in Chicago who wants to write short stories. However, he is forced to work as a technical manual writer for Pickering Industries, the fifth largest company in America, to pay the bills. Andy is shy and not good with women. He doesn't really want to be working at the company, though he is very good at his job.
• Jessica Green (played by Paget Brewster): Jessica worked with Andy for years before she became the head of Andy's department, and thus, his boss. They tried dating once, but it didn't work out. She often has to act as an intermediary between her superiors and Andy and his co-workers, forcing her to take sides. She is fairly superficial when it comes to men.
• Wendy McKay (played by Irene Molloy): Wendy is the receptionist at Andy's office. As of the pilot, she had only been working there a month. Andy is attracted to her, but found out that since he had not made a move in a month, Keith has started to date her.
• Byron Togler (played by Jonathan Slavin): Byron is a new illustrator who moves into Andy's office, which causes Andy annoyance in the pilot episode. Byron is fairly insecure and shy.
• Keith (played by James Patrick Stuart): Keith is Andy's best friend and co-worker and one usually sticks up for the other. He is the handsome guy in the office who has things handed to him because he's good-looking.

Pickering Industries is founded by Mr. Pickering (John Bliss) in 1880. Despite being over 170 years old, and dead, he appears in several episodes and has discussions with Andy within his imagination. His viewpoints are typically antiquated and contrary to political correctness to an extreme degree. His comments often seem to represent a negative aspect of Andy's mind, such as guilt, or self-doubt.

Teak (Charlie Finn) and Phil (Sean Gunn) live in the same building as Andy. They had been members of the same fraternity as Andy, ten years after Andy was a member. As such, they look up to him. It is hinted that Phil might be gay.

Conan O'Brien appears as Pickering's new CEO in the episode "Crazy in Rio." Other stars to have guest roles include Cedric Yarbrough, Jon Cryer, Molly Sims, Beth Littleford, Rick Peters, Bree Turner, Jarrad Paul, Rex Lee, Lola Glaudini, Patricia Belcher and June Lockhart, who plays Andy's grandmother.

The series' plots were fairly typical of sitcoms with Andy getting himself into a situation and having to find a solution. The unique aspects were several unusual devices that defined the show.

First was Richter's voiceover which essentially narrated the plot as well as Andy's thought processes in each episode. Secondly, and connected to the first, was Andy's imagination, which was presented onscreen as if it were reality until it was revealed in a smash cut accompanied by the sound of rewinding audio tape. This was often used to demonstrate alternatives to what actually happened for a given event. These fantasy sequences inspired the original working title, "Anything Can Happen," a sentiment Richter expresses in the series premiere's opening narration.