A range of well-known veteran Democrats, including Barrow and ex-Atlanta Mayor Shirley Franklin, have passed on a race to challenge Isakson. So have several considered to be rising stars in the party, such as Jason Carter, who ran for governor in 2014, and state Rep. Stacey Evans.
Even lesser-known contenders, including the Rev. Raphael Warnock and Michael Sterling, an official in Atlanta Mayor Kasim Reed's administration, have opted against a challenge after publicly wrestling over whether to run.
Ed Tarver, a former state senator who is now the U.S. Attorney in Savannah, told us in January he was also considering a run. He has declined to comment since.
Any Democrat who challenges Isakson will face daunting odds. The 71-year-old enjoys high name recognition, popularity across the aisle, solid relations with black leaders and more than $5 million in his campaign coffers.
Isakson has faced questions about his health since he revealed in June that he has suffered from Parkinson's for about two years. He has maintained that the disease was in its earliest stages and said it would not jeopardize his ability to serve another six-year term.
But some Democrats also see an opening if Donald Trump emerges as the Republican presidential nominee. They argue that Trump's candidacy has the potential to so infuriate Democrats and alienate mainstream Republicans that it could put an otherwise safe GOP Senate seat in play.
Isakson, in a recent interview, said he would support the GOP nominee whoever he may be. But he also made clear he wouldn't be easily tied to the billionaire.
“I have one position on 2016: I’m for Johnny Isakson.”
More: Read more about Isakson's reelection strategy.