Their ranks have been severely reduced in recent elections. Those who remain in politics have been marginalized by their own party, which has inexorably veered to the right in the past generation.
But now this beleaguered minority has an opportunity to wield outsized influence on what President-elect Barack Obama can accomplish in Congress.
Although Democrats made big congressional gains in the 2008 election, they are still a vote or two short of the 60-vote majority they need in the Senate to keep a tight rein on GOP filibusters that can easily gum up the works.
The support of just one or two moderate Republicans could be decisive in a close, party-line vote on issues such as union rights and economic rescue plans. So while there may be fewer moderates in Congress, they are in for a lot of attention.
"The power of moderates is declining in the country: They are fewer in number, and the country has polarized," said Thomas F. Schaller, a political scientist at the University of Maryland, Baltimore County. "But in any vote where you are down to one to two votes, there are always going to be people in the middle who have decisive power."
Vice President-elect Joe Biden and Obama's incoming budget director, Peter Orszag, have already met with Sen. Susan Collins, a Republican from Maine, about economic stimulus legislation. Obama's team has consulted Delaware's Republican Rep. Mike Castle, an expert on education, about school issues. Obama's choice for Secretary of Transportation - Ray LaHood of Illinois - was a moderate GOP leader in the House until he retired this year.
But if recent elections are any guide, being a moderate - one who supports abortion rights, for example, opposes the Iraq war, or supports labor unions - is hazardous to a Republican's political health. Swing voters have been alienated by President George W. Bush's policies and perceptions that the Republican Party is dominated by extremists.
The litany of Republican lawmakers who were defeated during the past few years includes centrists like Rep. Christopher Shays of Connecticut and Sen. Gordon Smith of Oregon, who were defeated in 2008. Retirees this year included moderates like Sen. John Warner of Virginia and New York's Rep. Jim Walsh.
In the House, where rules provide for strict majority rule, Democrats will have little need to court Republicans to pass most of their agenda. But in the Senate, a minority of 41 can filibuster to prevent a bill from coming to a vote. Senate Democrats will likely wind up with 58 or 59 members, depending on the outcome of a disputed Senate election in Minnesota.
The election results - by depleting moderate Republican ranks - leave the congressional GOP more dominated than ever by its more dauntless conservatives such as Sens. Jim DeMint of South Carolina and Tom Coburn of Oklahoma, who led the charge in the lame duck session that killed an auto industry bailout.
It remains to be seen how aggressively Republicans will try to wield the filibuster threat. They have recently signaled they will fight Obama's economic recovery plan if it moves too quickly. But there are political risks if the GOP is seen as obstructionist at a time when voters are clamoring for economic relief and change.