In the show, Dr. Cal Lightman (Tim Roth) and his colleagues in The Lightman Group accept assignments from third parties (commonly local and federal law enforcement), and assist in investigations, reaching the truth through applied psychology: interpreting microexpressions, through the Facial Action Coding System, and body language.

[10] The show is inspired by the work of Paul Ekman, a specialist on facial expressions and a professor emeritus of psychology at the University of California San Francisco School of Medicine.

Her innate talent in the field clashes with Cal's academic approach, and he often shows off by rapidly analyzing her every facial expression.

It was gradually revealed that Dr. Lightman was driven to study micro-expressions as a result of guilt over his mother's suicide.

She claimed to have been fine in order to obtain a weekend pass from a psychiatric ward, when she was actually experiencing agony (which parallels an anecdote in Paul Ekman's book "Telling Lies").

Rather than by force, they use careful lines of questioning, provocative statements, theatrics and healthy doses of deception on their own part.

Katherine Pope, former president of NBC Universal's TV studio, signed on as a consulting producer, working on the final four episodes of the first season.

However, he also commented "if this review were a face, Dr. Lightman would say it had a forced smile: hopeful, but dubious, about Lie's chances.

"[23] Tom Shales, writing for The Washington Post, said "Lie to Me seems an unusually meaty, thoughtful and thought-provoking crime drama – another police procedural, yes, but one with a dramatic and mesmerizing difference… easily one of the season's best new shows.

[26] The third season, which had its premiere moved forward to October 4, 2010, was viewed by 5.87 million people in the U.S.[27] The series' official cancellation was announced by Fox on May 10, 2011.

[33] The series was broadcast on Global in Canada, Network Ten in Australia, M-Net in South Africa, and also airs in Norway, Sweden, Iceland, Hungary and Belgium.