Monica Reyes was given up for adoption as a child, adopted by Mexican parents and raised in Mexico, having never identified her biological parents. Because of growing up in Mexico, Reyes speaks fluent Spanish.

She majored in folklore and mythology at Brown University, earning her bachelors and masters degrees in four years. In 1990, Reyes enrolled to the FBI at Quantico. Her first assignment in the FBI was serving on a special task force investigating Satanic rituals.

Reyes then served in the New York City field office, and also investigated the kidnapping of 8 year-old Luke Doggett, son of New York City police officer John Doggett. The boy was eventually found dead, but no suspect was ever apprehended. In 1999, Monica Reyes transferred to the New Orleans field office. She remained there until John Doggett, now an FBI agent, convinced her to accept a post on the X-Files FBI unit in Washington, DC, as his partner.

Monica Reyes is religious and a highly spiritual person, and has little doubt about the paranormal. She is not as obsessed with it as Fox Mulder is, but she is willing to accept explanations involving the paranormal, unlike John Doggett.

Is it highly probable that she began a relationship with John Doggett at the end of Season Nine, noticeably in the episode 'Release' Doggetts ex-wife comments on the two of them stating that, "He could have something really good with Monica, he just won't let her in" At the end of that episode him and Monica share a very intimate hug leading to believe that now John has got rid of his demons he can begin a relationship with Monica. Further to this, at the end of an episode closely afterwards 'Sunshine Days' we see the two of them holding hands, leading to belive that they have begun a relationship.