Brian and Stewie go on another road trip through alternate universes using a special remote control. Including a post-apocalyptic world, a parallel world run by dogs where humans are pets, and the Robot Chicken universe.

After finding a lump on her breast, Lois goes to the doctor to get it tested. Thankfully, the tests come back benign. However, the doctor looks into her family medical history and reveals that Lois is actually Jewish. Peter is eager at first for this new change, but after being visited by the ghost of his father, he changes his tune.

Spies Dan Aykroyd and Chevy Chase move into Cleveland's old house, while Brian and Stewie wind up in Russia following them.

When Brian starts dating an older woman named Rita, he becomes the laughing stock of the family. Things get worse however when Brian's date breaks her hip and Brian has to take care of her.

Stewie scores tickets to a Hannah Montana concert and discovers a surprising secret about the singer. Meanwhile, Chris captures the Evil Monkey that's been living in his closet.

Peter finds a baby who resembles Quagmire, and uses a Ham Radio to communicate with the ghost of Ronald Reagan, while Stewie clones himself.

Upset that Cleveland left the group of friends to move to Stoolbend, Virginia, Peter, Quagmire and Joe decide to interview potential friends to fill the vacancy. Meanwhile, Brian discovers that Quagmire hates him.

After much anticipation, Brian receives an invitation to an award ceremony celebrating his novel entitled Faster Than the Speed of Love, by the Rhode Island Society for Special Literary Excellence, convincing him that he is a great writer, until he discovers that the all the members of the book-reading club awarding him are mentally retarded.

Peter gives Lois' father, Carter Pewterschmidt, the bachelor party he never had, ultimately causing him to slip into a coma, that not even Dr. House, voiced by Hugh Laurie, is able to bring him out of. Lois is then given control and ownership of Pewterschmidt Industries, and Peter convinces her to let him run the company instead.

When Peter hits his head and suffers amnesia, he forgets everything about his life, including his family and friends. In an attempt to try to bring back his memory, Lois decides to reintroduce Peter to his old self, until he begins to hit on other women, much to Lois's dismay. She decides to take the kids and leave Peter, giving Quagmire the opportunity to score with Lois. Peter now must prove to Lois he can remember her and make himself worthy of her again.

Brian gets a job writing about the average American girl for a teen magazine. When he starts following Meg for research, he discovers that she fell in love with a man in jail named Luke.

When Brian and Stewie go missing for several days, Lois is at her wits' end until she sees a psychic who assures her they are safe. Even after the boys return home, Lois and Peter's psychic obsession continues, and Peter takes it a step too far when he starts charging neighbors for his extrasensory perception. Meanwhile, Chris develops a crush on a girl at school.