Author Existence Failure: Tony Jay's death means that whenever the films finally get made, they'll have to recast Megabyte.
The Danza: A unique example; the City of Adventure itself is named after the animation studio that created the show. In a more straightforward example, AndrAIa's original voice actress was Andrea Libman — different spelling, but pronounced the same way.
Dawson Casting: Averted. Young Enzo was played by a real kid and the production replaced the voice actor with another kid as their voice changed. One voice actor returned several years later to portray a different character.
Development Gag: In "The Medusa Bug" Phong explains that extended period being Taken for Granite by the Medusa Bug will eventually decompile low energy programs and up to high energy programs, showing an evolutionary chart of sorts displaying the hierarchy (street lamps - binomes - sprites). On the chart is a step between humanoid sprites and binomes of more blocky-looking humanoid form, which was the intended appearance of the main characters before they had the graphical power at what the show was eventually produced at.
Development Hell: The revival movie was announced on June 1st, 2008. As of April 2013, all that's come of that has been a teaser trailer and a single concept image, both released in 2009.
Doing It for the Art: Preceeding the Pixar revolution, the series was created as part of an untested medium. There were no animation or special FX studios at the time that could handle the rigors of a completely CGI series. Mainframe Entertainment was created for ReBoot, there was no Pilot Episode because the cost of equipment and other things required either a full season or nothing.
Executive Meddling: Many aspects of the show had to be changed due to censorship issues from the Broadcast Standards and Practices department at ABC. The creators understood at least some of the changes, even if they did not agree with themnote Bob not being allowed to jump through sheet glass made sense somewhat as it is possible to imagine a child imitating that and getting severely injured from it. However, some of the requirements were downright ridiculous. When celebrating Enzo's birthday, Dot (his sister) was not allowed to kiss him on the cheek since it was thought to be too incestuous. Ian Pearson, one of the creators, stated that he found the reasoning behind that decision "...one of the sickest things I've heard."
The show frequently lampshaded and lampooned the ABC censors and their decisions, with explicit references to the BS&P. There was even a song about it, set to the tune of YMCA by The Village People with lyrics that represented the writers' rants about Executive Meddling.
Also lampshaded in the note above. Instead of trying to figure out how to get Bob through the sheet glass, they teleport him through it by having Bob say "Glitch, BS&P."
Michael Benyaer voiced Bob in the first two seasons before Ian James Corlett took over in Seasons 3 and 4. However, in the fourth season, Benyaer returned to voice him for flashbacks, and also to voice the "second" Bob in the latter half of that season.
As a child, Enzo has been voiced by no less than five different actors. This was done because the creators wanted to have a child voice Enzo, so he had to keep getting re-cast. The fifth voice actor was used exclusively for the very young Enzo seen in flashbacks during season four.
Phillip Hayes voiced Hack in Season 1 and for most of Season 2. Scott McNeil took over from there and for the rest of the series.
Word of God: While not explained in the show until the fourth season, it was revealed by Gavin Blair after the second season episode "Gigabyte" that Megabyte and Hexadecimal were originally one supremely powerful virus, split into two more manageable forms. It makes the events of that episode a little more understandable.