When their parents go out of town for the weekend, Drake and Josh turn the house into a Bed and Breakfast after overhearing a vacationing couple say how they have no place to stay.
Drake and Josh compete against Megan in a salsa making contest so they can win a 45 inch plasma television. The boys soon discover Megan's secret ingredient and try to steal it for their own recipe.
Josh's email pal from abroad comes to visit. She spends most of her time paying attention to Drake, who doesn't return the favor until he finds out how rich she is. Knowing that she is homesick, Josh has a friendship ceremony performed between the girl and Drake but it really is a marriage ceremony.
Josh is confident that he will win the upcoming Science Fair, until his academic nemesis Mindy returns. He ends up taking second place again but ends up developing feelings for Mindy, and before long they are boyfriend and girlfriend.
Drake and Josh are worried that Walter is having an affair so they conspire to get to the bottom of it. They suspect that he is having an affair with a tv producer and sabotage of lunch that she and Walter are having. In reality, however, the lady is trying to help Walter get a better job and decides against it after witnessing his sons' behavior.
Drake breaks up with a girl he has been dating after she calls him her 'boyfriend'. Drake wants to see other people but then ends up changing his mind. Josh grows a mustache but this stops Mindy from kissing him.
Drake and Josh help their friend Helen after she has eye surgery and can't see. They visit her at home to help her around the house but when they see all the fancy electronics she has around, they take advantage of her temporary blindness to use all of her things.
When Josh breaks his foot and his parents have to take him to the hospital, Drake pretends to be a young doctor to impress the nurses. This backfires, however, when he is mistaken as a real boy genius doctor and is asked to perform the surgery on Josh.
Drake and Josh realize that they got into a fight against each other several years ago at a San Diego Padres game. Finding the foam finger that instigated the fight, they fight over it again.
Josh makes a horrible first impression when his girlfriend Mindy invites him to dinner to meet her parents so he tries to make it up to her by inviting them over to his parents' house. Meanwhile, Josh and his girlfriend wrestle to find out who is tougher.
Megan forces Drake and Josh to babysit her newly adopted pregnant sheep by promising not to pull any pranks on them for three months.
Josh is hired as a student teacher in Megan's classroom and challenges the kids to high level tests. Drake discovers an amazing drummer in the class and wants to recruit him, however when the drummer fails one of Josh's tests and isn't allowed extra curricular activities, Drake tries to get Josh fired.
To keep from being sent to remedial English, Drake agrees to mentor a young boy, however the boy prefers Josh to Drake.
Josh re-enacts the FBI's most wanted criminal 'The Theater Thug' on a tv crime show. Following his debut, he becomes mistaken for the real criminal and trouble ensues.
Drake, Josh and Megan are excited about the opening of a new rollar coaster called the Demonator. Their plans to ride it opening night are thwarted, however, when they have to watch over their grandfather. They enlist their friends to grandpa-sit for them but their grandfather mistakes them for WWII enemies when he wakes up from a nap and sees them.
Drake and Josh decide that they are through with the pranks that Megan plays on them so they turn the tables. They convince Megan that aliens are invading earth and that she will be kidnapped. All doesn't go according to plan.
Megan gives Drake and Josh two tickets to the "Dr. Phyllis Show" with hopes that they will stop their bickering. While on the show, the boys re-live all the crazy times between them but then later figure out that Dr. Phyllis is the mom of a girl that Drake dated so her intention wasn't to help them.