Incumbent Democrat Paul Sarbanes, Maryland's longest-serving United States senator, decided to retire instead of seeking a sixth term.

Democratic nominee Ben Cardin, a U.S. representative, won the open seat, defeating Republican lieutenant governor Michael Steele.

Ben Cardin, then a congressman since 1987, was the only other major candidate until September 2005, when former Baltimore County Executive Dennis F. Rasmussen, American University professor Allan Lichtman, and wealthy Potomac businessman Josh Rales entered the contest.

On August 31, 2006, Maryland Public Television (MPT) and the League of Women Voters (LWV) sponsored a debate between the two leading Democratic Primary Candidates.

[7] Michael S. Steele was expected to win the Republican primary, and the Baltimore Sun wrote the month before that he faced "only nominal opposition".

Third District Congressional Representative Ben Cardin won the Democratic Party nomination after facing tough competition in the contest for the Democratic ticket from former congressman and NAACP President Kweisi Mfume, businessman Josh Rales, former Baltimore County Executive Dennis F. Rasmussen, and several lesser-known candidates.

The evening was hosted by the Baltimore Urban League and moderated by Charles Robinson from Maryland Public Television and Doni Glover from BMORENEWS.

On the same day, incumbent Republican governor Bob Ehrlich lost reelection to Baltimore Mayor Martin O'Malley.