In Plain Sight was originally scheduled to premiere on Thursday, April 24, 2008, but USA Network held it back after the WGA strike delayed production of the summer series Burn Notice, pushing its debut to June 1, 2008.

The series was filmed on location in Albuquerque, New Mexico, the same city where its fictional WITSEC office is set.

Following creative differences with executive producer and series creator David Maples, USA Network used the 15th episode of season two as the season finale instead of the planned two-part ender, and Maples and co-producer Paul Stupin stepped down to become consulting producers, replaced by John McNamara.

The previously planned 16th episode of season two, meant to open season three, was shelved and replaced by a new opening episode written by incoming showrunner John McNamara.

Season three was reduced from 16 to 13 episodes when showrunner John McNamara took a medical leave of absence, with John Romano stepping in as executive producer to finish the season, ending on a cliffhanger.

Jeff Beal composed the series' theme song, while the score for the show changed hands over the seasons: W. G. Snuffy Walden for season one, Tree Adams for season two, and Evan Frankfort, Liz Phair, and Marc Dauer for the remaining seasons.

Will McCormack, who plays FBI Special Agent Robert O'Conner, is the real-life younger brother of lead actress Mary McCormack.

The pilot episode drew 5.25 million viewers, making it USA Network's highest-rated series premiere since Psych in 2006, and it outperformed Burn Notice's previous summer debut by 32% and the network premiere of Law & Order: Criminal Intent by 40%.