The program debuted in 1983, with former NBC anchorwoman Jessica Savitch as its host, but Savitch died later in the first season. Judy Woodruff took over as anchor in 1984, and hosted the show for five years. In 1990, the show did away with the anchor position, and left the narrator to introduce each report.

Every four years since 1988, Frontline runs a special profiling the nominees for President of the United States entitled "The Choice [Insert Year]" . The most recent of these aired on October 14, 2008, featuring a dual biography tracing the lives and careers of John McCain and Barack Obama produced by Michael Kirk.

Most Frontline reports are an hour in length, but some are extended to 90 minutes or beyond. Frontline also does occasional specials like "From Jesus to Christ", "The Farmer's Wife", and "Country Boys".

Since 1995, Frontline has been producing deep-content, companion web sites for all of its documentaries. The series publishes extended interview transcripts, in-depth chronologies, original essays, sidebar stories, related links and readings, and source documents including photographs and background research. Frontline has made many of its documentaries available via streaming Internet video, from their website.

Will Lyman is the distinctive voice who has narrated most of the series since its inception in 1983. However, certain reports have been narrated by David Ogden Stiers and Peter Berkrot.

Other Frontline reports focus on political, social, and criminal justice issues. Ofra Bikel, who has been a producer for Frontline since the first season, has produced a significant number of films on the criminal justice system in the United States. The films have focused on issues ranging from post-conviction DNA testing, the use of drug snitches and mandatory minimum sentencing laws, the plea system, and the use of eye-witness testimony. As a result of the films, 13 people have been released from prison.

After the September 11, 2001 attacks, the White House requested a copy of "Hunting Bin Laden". In 1999, Frontline had produced this in-depth report about Osama bin Laden and the terrorist network that would come to be known as Al-Qaeda in the wake of the 1998 United States embassy bombings. Following the September 11 attacks, Frontline produced a series of films about Al-Qaeda and the War on Terrorism. In 2002, the series was awarded the DuPont-Columbia gold baton for the seven films.

In 2003, Frontline and The New York Times joined forces on "A Dangerous Business", an investigation into the cast iron pipe making industry and worker safety. OSHA officials credit the documentary and newspaper report with stimulating federal policy change on workplace safety. In 2004, the joint investigation was awarded the Pulitzer Prize for Public Service.

Producer Michael Kirk's Frontline documentaries have won multiple awards. These films include Cheney's Law (Peabody Award, 2007), The Lost Year in Iraq (Emmy Award, 2006), The Torture Question (Emmy Award, 2005), The Kevorkian File (Emmy Award), and Waco the Inside Story (Peabody Award).

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