With the help of an out-of-this-world remote control, Stewie and Brian travel through alternate universes, including a post-apocalyptic world and a parallel world run by dogs where humans are pets.

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.

Chevy Chase and Dan Aykroyd move to Quahog. Brian and Stewie find out about their secret agency. They are told that there are Russian Sleeper Cells all over US. They go talk to Mayor West, and find out he is one of the sleeper cells. They follow Mayor West to Russia where they disable a nuke aimed at the US.

When Brian begins dating an older woman, the family begins to make fun of him. After Brian's new fling breaks her hip, he gets the pleasure of becoming her errand boy.

Father doesn't know best when Quagmire assumes responsibility for a baby left at his doorstep. Meanwhile, Stewie creates a stupid clone of himself that he uses as a slave. When he ends up creating a clone for Brian too, they find out that the clones are unstable, at which point the clones break down.

Peter and the guys interview potential friends to fill the vacancy left by Cleveland. Meanwhile, Brian discovers 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’ dad the bachelor party he never had, Mr. Pewterschmidt goes into a coma. Even Dr. House can't help. Lois gains control of Pewterschmidt Industries which she passes to Peter. He gets power-hungry and fires the board. Mr. Pewterschmidt bounces back and tries to regain control of what he’s built.

When Peter hits his head and suffers amnesia after getting in a fight with Richard Dawson on Family Feud, 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 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 out 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 cross-dresses in order to star in the American version of Jolly Farm Revue. Meanwhile, Peter makes Lois feel bad about her age.

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.

Lois encourages Brian to submit his pilot script to a network. James Woods gets involved and things don't exactly go according to Brian's original plan. Meanwhile, Stewie has a bit of a mishap.

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 150th episode, Brian & Stewie get locked in a bank vault, they are forced to deal with each other on a whole new level. Unlike any other FAMILY GUY episode, the acts will play out in real time as Brian and Stewie react to being locked in a small space with no baby food or martinis to keep them from losing their minds while they hatch an escape plan.

Quagmire can accept his dad's lifestyle choices, but not when they involve Brian.

Peter, Joe, and Quagmire search for the source of a dirty joke.

Peter makes good on another power outage at home--by entertaining his family with a retelling of Star Wars Episode V: The Empire Strikes Back. Newcomers to the story include Mort as Lando Calrissian, Chris' boss Carl as Yoda, and the Giant Chicken as the nefarious Boba Fett.