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On the flip side of the CSI effect, kidnap and rape victims are now known to leave their own DNA behind at crime scenes to give police forensic evidence to find. An example of this is how British serial sex attacker Jonathan Haynes was eventually caught. Haynes, who had avoided capture by forcing his victims to destroy forensic evidence was finally apprehended after the CSI effect was used against him when one of his victims ensured her DNA could be traced back to her attacker by spitting in his car and pulling out strands of her own hair. Her inspiration for this act? The CSI franchise.

Andy Garcia was originally offered the lead role, a character who would have been named Detective Rick Calucci. He declined the role, as did Ray Liotta. While in talks with franchise creator Anthony E. Zuiker about taking on the role of the lead character, Gary Sinise asked that the characters name be changed to Mac Taylor in memory of his brother-in-law, McCanna ("Mac") Harris, a decorated Vietnam vet who had died of cancer in the 1980s. (The "Taylor" is a nod to his most iconic character, Lt. Dan from Forrest Gump (1994)).

Several actors have had the chance to show off skills on-screen:

• Gary Sinise performs with a couple of members of his Lt. Dan Band at the end of Stuck on You (2006) and plays bass again at the end of Time's Up (2007). The guitars he uses are his own.
• In Tri-Borough (2005) there's a scene at an art gallery. Detective Kaile Maka (Kelly Hu) makes a remark about the artwork not selling well, and Danny Messer (Carmine Giovinazzo) says, "Yeah, I can see why," while nodding his head toward one of the paintings. The one he's indicating was actually painted by Carmine Giovinazzo (Danny Messer). Several of the other paintings in that scene are his as well.
• Giovinazzo also has a band, Cesau; it never appears on the show, but some of their songs are used in Sanguine Love (2010) which Carmine happened to write.
• Danny Messer claimed that he had a short-lived career in the music business, and that he quit baseball when he broke his wrist in a fight. Carmine Giovinazzo, who played Danny, admits that he quit baseball because of a back injury, and that he often brought his guitar to the set and played for his co-stars.
• Danny Messer's (Carmine Giovinazzo) tattoo is real.
• Several episodes have Melina Kanakaredes showing off her knowledge of fluent Greek. (Her parents are Greek immigrants and she and her family often visit the country).

In the real world, globally across most agencies, the equivalent CSI staff at a crime scene, and in the lab, would be wearing head to toe "forensic boiler suits", similar to those seen in microchip manufacturing clean rooms, to avoid contaminating evidence. The decision not to show the characters in these boiler suits is probably down to a creative decision for the audience to tell the characters apart.

The series began with Detective Mac Taylor (Gary Sinise) as a widower, and ends with him getting engaged to a new love interest. It is never revealed if he ends up getting married.