When Stan goes to Atlantic City for a bachelor party and is shunned by his so-called best friend, Roger steps in and becomes Stan's new sidekick. Their friendship goes to a whole new level, but when they return home and face Francine, Stan realizes that what happens in Atlantic City doesn't necessarily stay there. Meanwhile, Hayley and Steve team up to break up a good-looking couple.

Stan wants Steve to be popular and goes to desperate measures giving him steroids to make him bigger, better, and part of the in-crowd at school. But when the steroids have an unexpected side effect, Steve gets a lot more attention than anyone expected. Meanwhile, after Hayley makes a movie about Francine's life as a housewife, Francine is determined to start a new career as a doctor.

After Steve shows a lack of interest in Stan's job, Stan replaces him with Barry, Steve's malicious friend. Barry frames Steve to eliminate him from the household, but when Steve discovers Barry's weakness, he relies on his CIA skills to save the family. Meanwhile, Roger takes an impressive keg-stand and uses it to become a fraternity brother.

When Francine's birthday brings back haunting memories of a celebrity film moment stolen by George Clooney, Francine's new dream is to destroy the star. But when she tries to win Clooney's heart with the intention of breaking it, Stan actually falls for him and sabotages the plan. Meanwhile, back at home, Roger builds a vineyard and starts up a private sweat shop of foster children.

Stan realizes his own weight problem after he criticizes Steve about his new, overweight girlfriend, so he goes overboard with exercising, and develops anorexia. Steve realizes that his overweight girlfriend is the root of his father's problems, and he has to make a hard choice in an effort to save his father's life.

When Stan tries to trick Steve into attending summer camp, things go horribly wrong and Steve ends up in a refugee camp. However, Stan, being the eternal optimist, joins Steve and manages to stage a camp Olympics between the refugees and the rebel faction living across the river.

Stan loses his confidence, and his job, when a car salesman gets the best of him in a negotiation. Meanwhile, Roger and Steve set up a makeshift drive-in to try to get to first base with popular schoolgirls.

After Francine tells Stan she's looking for excitement in their marriage, Stan gets in the driver's seat and becomes involved in drag racing to spice things up. Meanwhile, Hayley breaks up with her boyfriend, Jeff, who is emotionally crushed until he joins Steve's world of online gaming. When Hayley finds out, she tries to sabotage their fun.

When Steve's new relationship with his girlfriend gives Francine empty nest syndrome, she tries to convince Stan to have another baby. Meanwhile, Roger tries to enroll in college with Haley in order to experience college life, but while Roger ends up teaching the class, Haley finds a new crush in her classmate Ethan (Elijah Woods), who turns out to be far from normal.

When Francine discovers Stan's secret, decades-old passion for competitive figure skating, she decides to be supportive and becomes his pairs partner until Stan's competitive nature gets the best of him and he ditches her for a new partner. Meanwhile, Steve's classmate Snot finds new respect among his peers when he parades his mail-order bride around the playground.

Stan has his heart set on speaking at the Republican National Convention on behalf of the Langley chapter, but when they pass him up for another candidate, he accepts the only endorsement he gets from the local chapter of Gay Republicans. While the people around him disapprove of his new lifestyle choice, Stan decides to follow his heart to speak on their behalf.

Roger og Steve bestemmer seg for at de ikke får nok intellektuell stimulans hjemme, og flytter til New York.

Stan vinner en konkurranse og får middagsbesøk av president Bush, men må konkurrere med familiemedlemmene sine som alle har sin egen agenda overfor presidenten.

Stan får besøk av «Ånden fra fordums tiders jul» og forandrer uheldigvis fremtiden når han prøver å bringe favoritt-høytiden sin tilbake til røttene.

Når Stan finner ut at alle naboene hans misliker ham, bruker han krefter i CIA for å få dem kastet ut. Roger og Steve begynner å svindle firmaer for penger med falske skadekrav.

Stan bestemmer seg for å følge drømmen om å leve av å lage festlige teddybjørner, men den nye forretningen hans forvandles snart til en business som ikke tåler dagens lys.

Når Steve nekter å leke med ham, finner Roger en ny bestevenn som begynner å mishandle ham. Stan og Francine prøver å redde Mr. Pibb fra å gå ut av produksjon.

Når Stan ordner en blind date for sjefen sin og den går fryktelig galt, tar han drastiske midler i bruk for å skjule sannheten for Francine. Rogers Kevin Bacon-imitasjon får katastrofale følger.

Når Stan tar feil og tror at en CIA-øvelse om atomkrig er noe som skjer på ekte, bestemmer han seg for å flytte familien til en fjerntliggende plass i fjellene for å overleve apokalypsen.

Steves research til en oppgave om George Washington Carver og peanøttsmør avdekker en sammensvergelse som stammer fra så langt tilbake som borgerkrigen.

En plan for å forvandle Steve og vennene hans til menn ender opp med at Stan blir tiltalt i en kongresshøring. Roger er forelsket i Hayley, og forårsaker en krangel mellom henne og Francine.

Francine demands that Stan take the family on a vacation after she learns all of their previous vacations never actually happened: The CIA had planted artificial memories of the "vacations" in their brains so Stan could ditch them. Meanwhile, Roger wants to be a thespian.

Når Stan får vite hvor mange sex-partnere Francine har hatt, mister han motet. De blir enige om skilsmisse slik at han kan ha uforpliktende sex med en annen kvinne, noe som får katastrofale følger.

Roger becomes a bounty hunter, and he and Stan race cross-country to turn in Jeff, who is wanted for smuggling pot into Florida.