In addition to politics, the show featured debate about non-political stories, such as the 2006 Duke University lacrosse team scandal or the death of Anna Nicole Smith, or one-on-one interviews with politicians, commonly with the host who most closely shared the guest's political ideology.

Fox announced on November 24, 2008 that Alan Colmes would leave the show at the end of the year, but he remained a commentator on Fox News, ran the blog Liberaland, and made occasional appearances on other programs like The O'Reilly Factor, and Shovio.com's TalkBackTV up until his death on February 23, 2017.

Ratings-wise, it was long the second highest-rated program in U.S. cable news behind The O'Reilly Factor and averaged 3.3 million viewers nightly for the Nielsen month prior to the 2008 presidential election.

[5] He sometimes took more conservative positions than other prominent liberals, such as supporting Rudy Giuliani for mayor of New York City and agreeing with the use of torture techniques by the government of the United States.

[6] Some of Colmes' liberal critics, notably commentators at Media Matters for America, praised him toward the end of the show's run, however.