When Hal and Lois go out of town for a "last chance" getaway before the baby comes, Reese has a big bash that gets out of hand. College-age thugs show up, cancel the party and set up a drug-making operation in the garage. All Reese and Malcolm can do is knuckle under. The good news is, Dewey's not around. The bad news is, his baby sitter is Lois's annoying co-worker Craig (David Anthony Higgins). Meanwhile, Hal and his very pregnant wife are off at a romantic retreat - feuding.
Malcolm is a regular high school kid trying to navigate his way through life despite the various obstacles thrown in his way a complete misunderstanding of girls, the constant burden of masterminding plans to get himself and his brothers into or out of trouble, and a miserable job at the Lucky Aide not to mention a severe case of teen angst.
Although Malcolm has a genius IQ, he can't seem to make sense of the opposite sex, much less his embarrassing family. Lois is the outspoken, opinionated mom, who still manages to rule the roost even though her boys are growing wise to her crafty ways. Hal, a dad who is just a bumbling, big kid at heart, often finds himself creating more chaos than his five boys combined.