Malcolm's family and scores of others are forced to relocate to a school gym because of a toxic-chemical spill caused by a derailed train. Seems it ran over an old couch that fell off Hal's car on his way to the dump. Amid the chaos, resourcefulness pays off for Dewey, who enlists sympathy by pretending his parents werehuged in an enveloping chemical cloud; and for Reese, who schemes to make money off the calamity. As the rascal puts it, "When people are miserable and suffering, it brings out the best in me".
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.