After the show ended, Bryan Cranston went on to be in the critically acclaimed series Breaking Bad. On the last season DVD of Breaking Bad, there is an alternate ending that involves Cranston playing as Hal waking up from a nightmare which happend to be the events of Breaking Bad.
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'.
The character of Francis would all but disappear from the show entirely starting with Season 6. For the final two seasons, Francis appeared in less than 10 out of the 44 aired episodes, despite the fact that Christopher Masterson remained in the opening credits. The character itself was changed significantly, going from the significant strides he had made to land a great job and become a responsible young adult, to once more returning to delinquent, manipulative and two-timing behavior. Christopher Masterson during this time took more of an interest in the production of the show, as he directed and wrote for much of Seasons 6 and 7 rather than starring as his character.
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.
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 (1993).
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.
When Francis was given a more diminished role in Seasons 6 and 7, the show changed focus entirely. Rather than splitting episodes between a Malcolm story with Francis side story, Hal and Lois instead became the primary focus of the show, with side-stories being reserved for Malcolm, Reese and Dewey. Francis no longer appeared in his own stories and instead became only an occasional recurring character.
Scenes from One Million Years B.C. (1966) 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.
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". There are no indications that the family has a last name, except in the pilot when Francis is talking on the phone to his family, you can see his name tag on his Marlin Academy uniform is "Wilkerson", but people often joked and called the family "Nolastname".
Many of the side characters played "double roles". For example in season 1 the epidode therapy Ms Gilbert the school therapist is also the administrator in the episode church later on in the series in season 4.
The episode Family Reunion involves Brenda Strong, who plays Mary Alice Young on Desperate Housewives. In Malcolm defends Reese Katheryn Joosten costars. She plays Karen McCluskey in Desperate Housewives.
In the two part episodes "Company Picnic" there are several big name guest stars. One of them being Jane Kaczmarek's then-husband Bradley Whitford, who starred as Joshua Lyman in the series The West Wing.