- Acting for Two: A lot of the time, due to having Loads and Loads of Characters.
- Richard Horvitz, outside of voicing Orthopox, also voices the suburban crazies and The Freak.
- J. Grant Albrecht, who plays the main role as Crypto, voices the urban crazies, urban males and the G-men. He also voices the thinly-veiled Jack Nicholson parody in Path of the Furon.
- Actor Allusion:
- Not confirmed, but it seems like it shouldn't be a coincidence that Richard Steven Horvitz is cast to play the ornery alien invader who is in charge of a mission on Earth. Perhaps to drive the reference home further, concept art shows Crypto's backpack was originally to have four spider-like mechanical legs folded away inside.
- In the Japanese version, the Major is voiced by Atsuko Tanaka. Take a good guess why.
- This isn't the first time Edita Brychta played an attractive Asian woman.
- Fake Nationality:
- From Destroy All Humans! 2 onward due to the usage of non-American characters. Justified as most of the actors being American.
- Fake Brit: Actually averted and played straight with Albion NPC characters in Destroy All Humans! 2. While Edita Brychta and Robin Atkin Downes are British actors themselves, every other actor are all American.
- Franchise Killer: A twin-killing, as Big Willy Unleashed (Wii) and Path of the Furon (PlayStation 3 and Xbox 360) got hit with mediocre-to-bad review scores. However, Nordic Games (the current owner of the series) has expressed interest in reviving it, beginning by re-releasing the first two games on PlayStation 4 and making the first game backwards-compatiable on Xbox One. In 2019, they announced that a remake of the first game will be coming in 2020.
- No Export for You:
- While the first game did get a (heavily edited) Japan release, none of the later games in the series were released there.
- There is a Playstation 3 Version of "Path of the Furon", but it was released for PAL regions only.
- The Other Darrin: A pay dispute rendered J. Grant Albrecht and Richard Horvitz (the voice actors of Crypto and Pox) unable to voice their respective characters during Big Willy Unleashed, with Sean Donnellan and Darryl Kurylo replacing them as the voices. Albrecht and Horvitz would later return for Path of the Furon.
- Real Song Theme Tune: The trailer for the remake has Crypto brainwashing people set to "Ich Will" by Rammstein.
- Role Reprise: For the 2020 remake of the first game, Richard Horvitz returned to voice new lines for Pox. Based on the demo, it's very easy to figure which lines are new and which were recycled from the PS2 version, namely the new lines have a higher sampling rate and Pox's voice is less gravelly and more flamboyant.
- What Could Have Been: In 2006, a TV sitcom produced by the producer of King of the Hill and based on this game was planned. It was scrapped soon after the production of the second game. Oh the possibilities...
Trivia / Destroy All Humans!