And that could mean potentially crowded field to replace him.
Former presidential candidate and restaurateur Herman Cain would likely be an early frontrunner, polling has showed. But Cain said Friday that he would not run. Former House Speaker Newt Gingrich also said he won't make a bid.
Given the interest in this race even before Chambliss decided to retire, and the lack of an obvious frontrunner, we could soon see a number of candidates line up for the seat, especially on the Republican side.
Here are some Democratic and Republican names to watch, in alphabetical order, by party:
* Paul Broun: Rep. Broun said this week that he was "honored" that people were asking him to challenge Chambliss, but had not made any decisions about the race.
* Erick Erickson: Yes, The conservative blogger has already said he will not run for Senate, so it's unlikely that he will reverse course. But Chambliss's retirement changes the picture, and so we are including him as someone worth at least keeping an eye on.
* Karen Handel: The former secretary of state was reportedly considering a challenge to Chambliss late last year. A conservative, Handel narrowly lost the race for the 2010 GOP gubernatorial nomination against now-Gov. Nathan Deal (R). If she runs, look for her former involvement with the Susan B. Komen Foundation and the surrounding controversy over a decision to cut Planned Parenthood funding (it was subsequently reversed) to reemerge. Handel's initial support of the decision could help her among social conservatives.
* Sonny Perdue: The former two-term governor would have a natural name ID advantage over many contenders. That alone means it is worth mentioning him. On the flip side, he's 66 years old, and may not want to mount another statewide bid.
* Tom Price: Congressman Price's conservative chops -- he formerly chaired the Republican Study Committee -- and well-stocked war chest would make him a candidate to watch if he runs. One note: It's hard to imagine both Price and Handel running, since Price supported Handel in her gubernatorial bid.
* Lynn Westmoreland: Recently tapped to be deputy chairman of the National Republican Congressional Committee, Westmoreland represents a districts that stretches to the southwest from the Atlanta suburbs.
* John Barrow: The conservative Democratic congressman defied the odds in a tough district in 2012, and 2014 is already looking like an uphill climb. Barrow's conservative profile and the toughness of winning reelection may prompt him to at least give the Senate race a look.
For now at least, Barrow sounds like he is staying put. “At this time, I have no plans to run for anything other than re-election in the 12th district, but I am certainly gratified that people have been suggesting I run for the Senate," he said in a statement
* Max Cleland: A decorated Vietnam war veteran and one-term senator, Cleland lost his seat to Chambliss in 2002. He served as secretary of state for 14 years before joining the Senate.
* Kasim Reed: The Atlanta mayor, who has roots in the state legislature is worth watching on the Democratic side. He's a rising Democratic star who heads the state's largest city.
-- Chris Cillizza contributed