With the help of an out-of-this-world remote control, Stewie and Brian travel through alternate universes, including a post-apocalyptic world, a parallel world run by dogs where humans are pets and a "Robot Chicken"-like existence.
When Lois finds a lump on her breast, she goes to the doctor to test for cancer. The tests come back benign, but the doctor looks at her family medical history and reveals some news about Lois' heritage. Peter takes to the family's newfound faith eagerly, but when he is visited by the ghost of his father, he changes his tune. After a visit from an old friend sets him straight, Peter and Lois agree to go back to the way things were.
Stewie and Brian are suspicious when two guys move into Cleveland's old house, and when they find out Dan and Chevy are spies and they have dossiers of all the people in Quahog they follow them on a mission to Russia and end up in hot water .
When Brian snags an older woman, he becomes the laughingstock of the family, but things go from bad to worse when she breaks her hip and Brian has to be her errand-boy.
When Stewie scores tickets to a famous teen pop singer's concert, he ends up meeting and becoming great friends with her, but things get weird when he discovers one of her darkest secrets. Meanwhile, Chris tries to prove to the family that the Evil Monkey is real.
When Quagmire assumes responsibility for a baby who looks just like him, he quickly realizes he may be in over his head. Meanwhile, Stewie clones himself in order to have a personal assistant.
Feeling blue, Peter and the guys interview potential friends to fill the vacancy left by Cleveland. The interview process leads them to Jerome but things don't look so good when it's discovered that Quagmire hates him.
When Brian accidentally kills another dog he is surprised to see that no one cares so he tries to convince everyone that the life of a dog should have the same value as a human one. Meanwhile, Lois hires a maid who doesn't listen to Peter.
When Peter gives Lois' father the bachelor party he never had, Mr. Pewterschmidt slips into a coma and not even Dr. House can bring him out of it. With her father incapacitated, Lois is given control ofPewterschmidt Industries. Peter convinces Lois to let him run the operation, but he gets power-hungry and fires the board. Mr. Pewterschmidt soon bounces back and tries to regain control of what he's built - even though it may be more difficult than Christmas shopping for Peter -.
After Peter hits his head and develops amnesia, he forgets everything, including his family and his friends. Lois takes extra care of Peter and tries everything to jog his memory and until he starts hitting on other women. Fed up with his antics, Lois takes the kids and leaves, giving Quagmire his opportunity to swoop in and score.
Brian gets a gig writing for a teen magazine about the average American girl, but when he starts trailing Meg for research he discovers that her desperate attempts at dating have led her to a guy in the slammer. When Brian tries to expose Meg's secret to the family, he finds that her boyfriend, Luke, has broken out of jail and has been hiding in the Griffin's house.
When Chris and Stewie go missing for several days, Lois is at her wit's 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.
Stewie wants to audition for his favorite show, "Jolly Farm," but when he finds out they are only auditioning little girls, he creates and alter ego by dressing up a la "Tootsie." Meanwhile, Meg finds herself a normal guy to date and shocks the entire city of Quahog.
After Peter has some luck selling footage of a celebrity he caught off-guard, he decides to become a full-time paparazzo. To make matters worse, his new boss, Angela, finds him irresistible and plagues him with unwanted advances. When Peter rebuffs her, he winds up getting the ax. Meanwhile, Stewie makes his theatrical debut in a school play, only to be overcome with stage fright.
When Lois reads Brian's pilot script, she falls in love with it and insists that he meet with network executives to pitch it. The execs respond positively, and the initial casting session goes well with Elijah Wood auditioning for the lead role. But when the suits insist that Brian hire James Woods and change the entire concept, Brian finds himself caught between a rock and a hard place. Meanwhile, Chris and Meg seriously injure Stewie and try to cover it up.
When the local news announces that the Earth will be destroyed by a black hole in 24 hours, everyone in Quahog goes nuts trying to live out their last day.
In the Special 1-Hour 150th Episode Event, Brian and Stewie get locked in a bank vault where they are forced to deal with each other on a whole new level.
Quagmire gets the surprise of his life on Mother's Day, when his father starts to go through the change of his life.
Peter, Quagmire and Joe search to find the source of all dirty jokes leads them to Virginia, where they reunite with Cleveland and meet his new family,.
In the one-hour season finale, FAMILY GUY's homage to the "Star Wars" saga continues with a retelling of "The Empire Strikes Back".
Lois agrees to become a surrogate mother for a friend who is unable to conceive a child of her own. But when the friend and her husband are killed in a car accident, Lois and Peter consider whether to terminate the pregnancy.