Ironically, David Krumholtz (who failed Algebra I twice, and hated math in school) plays a mathematician, while Dylan Bruno (who graduated from M.I.T. with a math-heavy engineering degree) plays the math-challenged F.B.I. Agent.
Navi Rawat's character is named "Amita Ramanujan", a reference to Srinivasa Ramanujan, a self-taught Indian mathematician, who worked in the first two decades of the twentieth century, most notably collaborating with G.H. Hardy in number theory.
Despite his character's genius on the show, David Krumholtz calls himself a "math idiot." He received math crib sheets to study along with the scripts that were prepared by Caltech professor Gary Lorden.
"Cal Sci" (or the California Institute of Science) is modelled on the California Institute of Technology (Caltech) in Pasadena, developing characters loosely based on a Caltech professor and students. Portions of the series have been filmed on the Caltech campus. Gary Lorden, the chairman of the math department at Caltech, consulted for the show. The pilot episode was screened at Caltech as well, receiving a standing ovation at the end.
Charlie's (David Krumholtz's) picture, from his old high school year book, is actually a publicity still from 10 Things I Hate About You (1999).