Mesa, Arizona (CNN) -- The final four major Republican candidates are facing off in their 20th debate of this year's election cycle and their first in 27 days.
Former Massachusetts Gov. Mitt Romney, former Sen. Rick Santorum of Pennsylvania, former House Speaker Newt Gingrich and Rep. Ron Paul of Texas last met on January 26 before the Florida primary. Romney went on to win big there and in Nevada, while Gingrich, who had just scored an impressive victory in South Carolina, faded fast.
Then Santorum surged in state and national polling after sweeping the February 7 contests in Colorado, Minnesota and Missouri.
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The debate Wednesday is the last time the candidates are sharing a stage before primaries in Arizona and Michigan on Tuesday, before Washington state holds a contest on March 3, and before 10 more states hold primaries or caucuses on March 6. And no more debates are currently scheduled. CNN canceled a debate in advance of Super Tuesday after Romney, Santorum and Paul pulled out.
Santorum, once a long shot, tops national polling and is neck-and-neck with Romney in the latest surveys in Arizona and Michigan.
"There's not much room for error at the top of a pyramid," said Candy Crowley, CNN chief national correspondent and host of CNN's "State of the Union." "This will be Santorum's first time ever center stage, where the front-runner stands and gets pummeled."
There will be plenty for him to be pummeled over, one GOP strategist said.
"This will be the first debate where Santorum is the main attraction. The attacks should come from all three other candidates," said Gentry Collins, a former political director for the Republican National Committee and the Republican Governors Association
"And both Santorum's campaign staff and his super PAC have provided plenty of fodder in the last few days to add to a Senate voting record he will be forced to defend."
"The fundamental question coming out of this debate is whether Santorum will look like the pre-South Carolina Gingrich, with strong responses, commanding presence and rallying the base around unfair attacks, or whether he'll look more like the pre-Florida Gingrich, who appeared weak, petty, trying too hard and failing to rally a base to himself," added Collins, who steered Romney's campaign in Iowa four years ago but who is not backing a candidate this cycle.
Another strategist says Santorum has created a challenge for himself.
"Santorum has been improving every debate, but this time he has set a trap for himself on social issues, including contraception, prenatal care and the president's faith," CNN contributor Alex Castellanos said. "If he can't refocus this debate on Romney and the economy, Santorum will marginalize himself as fringe candidate with no real chance to beat Obama in the general election."
Romney, who will be sitting next to Santorum at the center stage, has just as much on the line.
"Mitt Romney has been running as the vanilla candidate of the GOP establishment. His problem is that no Republican voters are marching in the streets shouting 'we want vanilla!' " said
Castellanos, who was a top media adviser for Romney's 2008 nomination bid but who is not taking sides this cycle. "But if Santorum continues to marginalize himself in this debate with wacky positions on social issues, vanilla will sell because it's the only flavor Republicans have left."
Castellanos said Romney needs to engage with Gingrich to stop Santorum.
"He needs to give Gingrich a moment to shine," he said. "Romney hasn't been able to put Santorum away himself. The best weapon in Romney's arsenal to deter Santorum is 'Newtonium.' "
The debate may be Gingrich's last chance for a breakout performance before a national audience.
"The Arizona debate is an oasis for Gingrich's regularly in-debt campaign. An audience of millions for the price of a plane flight and a hotel room. And debates are usually terra firma for Newt who has an instinct for the jugular and a way of channeling the angry, frustrated Republican right," Crowley said. "Like Santorum once needed Gingrich to fall, Gingrich now needs Santorum to collapse under the weight of expectations for a frontrunner."
Of all the candidates, Paul might have the least on the line. Thanks to his enthusiastic and devoted supporters, a strong debate performance is probably not as crucial for Paul as it is for the others.
The timing for tonight's debate couldn't be any better for Arizona and the Republican governor, Jan Brewer, says that the showdown is very important to her state.
"I think that Arizona will be a pivotal state. There are a lot of undecided voters in Arizona so I think that people will be tuned in and watching, and because of this debate will be making their decision, not only in Arizona but across the country," Brewer said.
And what do Arizona voters want to hear from the candidates?
"I think that just like everywhere in America, people are concerned about jobs and the economy. Here in Arizona people are also concerned with their border security, they are concerned about new federalism and states' rights, and are very interested in natural resource issues," Brewer said.
While some of the questions were to be those of interest to Arizona voters might want to hear asked, questions from moderator John King, CNN's chief national correspondent and anchor of "John King, USA," the audience and social media will break other ground.
"It shouldn't surprise anyone to hear that we might ask about immigration or the economy, both of which are important subjects for Arizona Republicans," said CNN Washington Bureau Chief Sam Feist, the executive producer of the debate. "We're also going to try to ask questions on subjects that haven't been discussed as frequently in the previous 19 debates."