"Krelboyne", the name of the class of gifted students to which Malcolm belongs, is taken from the name of the nerdy hero of The Little Shop of Horrors.
The animation clips shown briefly during the opening credits are from the Japanese anime Nazca (JP).
Scenes from One Million Years B.C. can be seen during the opening credits. In one of them Raquel Welch is shown in the claws of a monster bird. The other scene shows the fight against a giant turtle.
On the show, Reese is the second oldest brother of Malcolm, but in real life Reese (Justin Berfield) is less than three months younger than Malcolm (Frankie Muniz).
The two wrestlers briefly featured in the opening credits are Bret Hart and Chris Benoit.
The hamster that Dewey releases in an earlier episode can be seen in various episodes after, rolling past the screen (in its exercise ball) on the ground in the background.
In the episode where Hal and the boys go to the race track, they come home to discover that Lois had gone through all of their stuff, in that pile was a pack of Morley cigarettes, the same fake brand the Cigarette Smoking Man prefers to use on The X-Files.
Merrin Dungey (who plays Stevie's Mom, Kitty Kenarben) appeared in the first episode as Malcolm's teacher.
Jane Kaczmarek in real life has given birth by way of Caesarian section three times. When it came time to simulate giving birth without a C-section in the episode Baby Part Two, Jane just imitated every other birth she had seen on television.
Two of the Krelboynes, Dabney and Lloyd, are named after student houses at Caltech.
In the original version of the show Otto Mannkusser and his wife are Germans, in the German dubbed version they are Danes.
The monster seen rising from the water in the opening credits is the monster from Clash of the Titans
In the episode where Hal takes the boys to the race track, it's revealed that Malcolm was named after Hal's favorite NASCAR driver, Rusty Malcolm.
The character of Reese was ranked #9 in TV Guide's list of "TV's 10 Biggest Brats" (27 March 2005 issue).
The motto of Lucky Aide is: The "L" Stands for Value.
In the opening credits, the boxer who inadvertently knocks out the referee is Pedro Cardenas, fighting Willie deWit. He accidentally KO'ed referee Bert Lowes during the 1982 North American Championships in Las Vegas.
The signs in Dewey's Busey classroom read, "Put ups - not put downs," and "Words not hands."
FOX announced that this program will air its final (151st) episode on 14 May 2006.
Actor Patrick Bristow first appears in the Episode "Ida's Boyfriend" as Phillip, the head of the Acting troupe hired to hold a Murder Mystery at the Grotto. Later, Patrick Bristow returns to the show as Lloyd, Chad's Father in the episode "Chad Sleep's Over".
None of Malcolm's family have a last name. While in military school, Francis was referred to only as "Francis" and never by his last name. Reese joins the army and we learn the last name of his fake ID is "Jetson" but there is no indication that that is his real name.
The family's last name was in fact revealed in the pilot as Wilkerson. It's on Francis's name tag when he calls home about his allowance.
Unusual for a live-action sitcom, the show featured no laugh track.
Although the family's surname was revealed as Wilkerson in the pilot episode, it was decided afterwards that the family shouldn't have a last name. A running joke on set was that the family's last name was 'Nolastname'. This is officially confirmed in the final episode "Graduation" when Francis drops his work pass and his surname is briefly seen. Further confirmation can be seen when Malcolm is introduced to the stage for his speech. His last name is not heard as the microphone screeches at the crucial moment but you can read the announcer's lips clearly saying 'Malcolm Nolastname'.