- Author Existence Failure: In 2003, Jaclyn Linetsky, the voice of Lori (as well as the title character of Caillou and Megan O'Connor on 15/Love), died in a car accident. On What's With Andy? and Caillou, her characters were recast; 15/Love went in a different direction.
- Channel Hop: In the United States, the show went from Fox Family (later ABC Family) for its first season to Toon Disney for its second and third season, airing on the channel until the Disney XD rebrand.
- The Danza: After being recast, Danny was voiced by Danny Brochu.
- Keep Circulating the Tapes: Though it ran in Canada and internationally for quite a while, the show never saw a true DVD or VHS release in North America (though some DVD releases with an English audio track made it to the Czech Republic); a few episodes were released on videotape in Canada as a double feature with The Kids From Room 402, which are exceptionally hard to find.
- The Other Darrin: The first season was recorded in Los Angeles, while the other seasons were recorded in Montreal, Canada due to Disney's acquisition of Fox Family and Saban. The only cast member who wasn't replaced was Ian James Corlett (Andy), who was a Canadian citizen. For instance, Dee Bradley Baker, who originally voiced Andy's dad and Martin Bonwick, was replaced in those roles by Arthur Holden and Michael Yarmush, respectively- Mr. Ratburn and Arthur's original voice.
- Similar to Corlett in English, the only cast member who wasn't replaced in the Latin Spanish dub was Enzo Fortuny as Andy.
- Production Posse: Upon the move to Montreal, several actors from other CineGroupe productions, including Terrence Scammell and Rick Jones, came on board.
- Technology Marches On: A few of the pranks are quite dated to the show's early 00s period:
- "Beat the Bomb"'s entire plot kicks off due to Danny mixing up audio tapes in a prank call. Today, it'd be quite easier to do it using a computer, cell phone or soundboard to play sound effects.
- "TeenDreamboats" is based on Andy fooling the entire town into thinking a fake popular band is going to play on stage at a festival. Suffice to say just a few years later, anyone would first turn into searching the internet for a supposedly popular band.
- "A Match Made in East Gackle" has Lik and Leech fooled into sending romantic e-mails to each other. Over time, instant messaging and social media became more viable, making such a prank harder to pull off.
- "Food for Thought" has Andy trick each warring restaurant's owner into thinking their home country lost at a foosball championship. Not only the painstaking process of editing existing TV footage through using a dual VCR setup become obsolete through easy access to video editing on just any computer, spoofing TV signal through hacking into the antenna would also have to take different form due to the retirement of analog television.
- Unfinished Dub: The Latin American Spanish dub only covers the first 2 seasons, it's unknown why they didn't dub the 3rd season.
Trivia / What's with Andy?