He played in Major League Baseball (MLB) for the Arizona Diamondbacks, San Diego Padres, Oakland Athletics, New York Mets, Chicago Cubs, and Washington Nationals.

[5] During his first game as a San Diego Padres starter (August 3, 2007), Hairston hit two consecutive home runs.

He was particularly tough against the Giants, with 11 of his 58 career homers coming off San Francisco, as well as 23 RBI, by far the most against any team he's faced.

[7] Hairston hit a home run to break a 6–6 tie in the top of the 13th inning against the Colorado Rockies in the 2007 Wild Card tie-breaker game.

[8][9] On July 5, 2009, Hairston was traded to the Oakland Athletics for Sean Gallagher and minor leaguers Ryan Webb and Craig Italiano.

On January 16, 2010, Hairston was traded back to the Padres, along with outfielder Aaron Cunningham in exchange for third baseman Kevin Kouzmanoff and minor leaguer Eric Sogard.

On July 7, 2013, Hairston was traded to the Washington Nationals for minor league pitcher Ivan Pineyro.

[15] Used mostly off the bench in 2013 with Washington, he did start in left field against most left-handed starters, spelling Bryce Harper or Denard Span.

On November 18, 2015, Hairston signed a minor league contract with the Chicago White Sox organization.