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 a universe reminiscent of the show Robot Chicken.

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.

Chevy Chase and Dan Aykroyd (starring as themselves) move to Spooner Street and hit it off with the Griffins culminating in Stewie and Brian becoming involved with a spy mission in Russia.

Brian dates an older woman despite the ribbing he gets from his family.
It only gets worse when he's forced to become her errand boy after she breaks her hip.

Stewie attends a concert of a teen superstar and discovers a surprising secret about the singer.

Meanwhile back at home, Chris tries to prove to the family that the Evil Monkey is real.

Father doesn't know best when Quagmire assumes responsibility for a baby Peter finds who looks just like him.

Meanwhile, Stewie clones himself in an all-new episode that also features a guest voice by Brittany Snow.

NBA Champion Kevin Garnett of the Boston Celtics guest-voices when Peter and the guys interview potential friends to fill the vacancy left by Cleveland.

However, things don't look so good for Garnett when it's discovered that Quagmire hates him.

After Brian accidentallyhugs another dog, and no one seems to care, he tries to convince everyone that they should value the life of a dog the same as a human. 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 (guest voice Hugh Laurie) can bring him out of it.
With her father incapacitated, Lois is given control of Pewterschmidt 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 hitting his head, Peter 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. Having had enough of his antics, Lois takes the kids and leaves.

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 pulls a "Tootsie" in order to star in the American version of Jolly Farm Review.

Meanwhile, Peter makes Lois feel bad about her age, and she gets a bit jealous of Meg’s new boyfriend.

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 150th episode, Brian and 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.

Lois agrees to become a surrogate mother but the couple of the child she's carrying dies and she's forced to make a decision whether or not to terminate the pregnancy.