Most of the playful banter between Derek Morgan (Shemar Moore) and Penelope Garcia (Kirsten Vangsness) stemmed from the way the actor and actress talked to each other in real life.
The entire cast have mentioned that they are like one big family. Joe Mantegna calls Shemar Moore and Matthew Gray Gubler his "golden boys".
Matthew Gray Gubler does not wear matching socks, because he thinks it's unlucky. In a few of the episodes, you can see his mismatched socks.
David Rossi has mentioned he knows Sir Ringo Starr. There is even a picture of him and Starr on Rossi's desk. Joe Mantegna and Sir Ringo Starr are friends in real life.
The character "Penelope Garcia" was supposed to be in only one episode, but she tested so positively that she was added to the main cast, and has the highest appearance count appearing in all but one episode (Season 1 Episode 5; "Broken Mirror").