Here are five things to watch for during the debate at Dartmouth College in Hanover, New Hampshire.
CAN RICK PERRY END HIS STRING OF BAD PERFORMANCES?
Perry, the Texas governor, will be under the most pressure to perform well after a series of stumbling debate showings sent his campaign into a nosedive.
Perry led the field upon entering the race in August but fell back in the pack after he was attacked by rivals last month for supporting cheaper in-state tuition for illegal immigrants and for ordering young girls be vaccinated for a sexually transmitted virus.
Perry's $17 million fund-raising take in the third-quarter showed he has the finances for the long haul, and a more forceful and steady performance would begin to reassure potential supporters.
CAN HERMAN CAIN CONTINUE HIS HOT STREAK?
The former pizza executive is on a roll in opinion polls, surging into the top tier of the Republican race since his surprise win in a Florida straw poll last month.
But the political newcomer has not faced the scrutiny of his policies or criticism of his rivals that is sure to come if he stays hot.
The debate, which will focus on economic issues, could raise questions about Cain's signature 999 tax plan that would scrap existing tax codes for a flat nine percent corporate, income and sales tax.
Some experts say the sales tax portion of the plan, which would be in addition to state and local sales taxes, could shift a heavier burden to lower-income earners.
WILL ROMNEY BE A TARGET FOR RIVALS?
Perry's decline opened the door for rival Mitt Romney to regain his lead in opinion polls of the Republican race. Romney, the former Massachusetts governor whose 2008 White House bid failed, had been the leader until Perry rolled by him.
Romney is a smooth and experienced debater who has largely gone unscathed in previous showdowns as candidates focused on other targets, but he might not be able to escape the spotlight this time.
His support for abortion rights and a healthcare mandate while governor of Massachusetts -- he now opposes both -- make him an object of suspicion for many social and religious conservatives.
His Mormon faith also raises questions for some evangelical Christians. A Texas pastor who supports Perry put those questions in the spotlight last week when he said he believed Mormonism was a cult. Perry distanced himself from the remarks.
CAN JON HUNTSMAN MAKE A LAST STAND?
Time is running out for the former Utah governor and U.S. ambassador to China, whose campaign has failed to catch fire. Conservatives do not like his moderate stances on climate change and his support for civil unions for homosexuals.
Huntsman still lags in low single digits in national polls but has shown some slight improvement lately in New Hampshire, where he has staked his campaign on a strong showing.
The debate will be a vital opportunity for him to make a splash in his make-or-break state.
WILL ANY OF THE OTHER CONTENDERS SURFACE?
With less than three months remaining before the first nominating contests, some of the longshot contenders are running out of chances to make an impression on voters.
Libertarian U.S. Representative Ron Paul is a forceful debater with a dedicated following, but is still trying to break through to the broader electorate. Conservative U.S. Representative Michele Bachmann has sunk back to earth after rising in the polls through the summer.
Former U.S. Senator Rick Santorum and former House Speaker Newt Gingrich are also strong debaters with years of experience in national politics, but if they are going to catch fire they need to do it soon.