It's the first forum since Trump won seven states on Super Tuesday, solidifying his status as the candidate to beat in the Republican field. It's also the first debate since last week's raucous insult-fest in Houston.
Here are four big things we'll be watching for tonight:
What Will Marco Rubio Do?
Last week's debate marked the beginning of Rubio 2.0 — the Florida senator's shift from portraying himself as an above-the-fray, ideas candidate to becoming an attack dog focused on Trump. On the Houston stage, Rubio hit Trump for hiring immigrants who were in the country illegally to build Trump Tower, fraud allegations against Trump University, and a lack of details in the real estate mogul's proposals.
And that was only the beginning. In the next few days, Rubio mocked Trump's tan, suggested Trump wet his pants and made jokes about the size of Trump's hands.
Attack Dog Rubio was a hit with crowds at his events. But aside from a win in Minnesota's caucuses, Rubio had a lackluster night Tuesday. He finished second in just one other state, Virginia. In Texas, Vermont and Alabama, he failed to crack 20 percent, the cutoff for collecting a share of statewide delegates.
Rubio continued his attacks on Trump during his Tuesday night appearance, calling the front-runner a "con artist."
The question is whether Rubio sticks to his guns tonight or reverts back to the policy-packed, general election-geared sound bites he stuck to in nearly every other debate this campaign. In a fundraising email sent out Wednesday night, the Rubio campaign indicated it will be the former: "Tomorrow night, about 24 hours from now, I look forward to doing more of the same and once and for all exposing [Trump] for the con artist he is."
How Will Trump Respond To Megyn Kelly?
The debate is airing on Fox News, which means Megyn Kelly will be moderating. Trump has feuded with many people in the course of his campaign — even Pope Francis — but his attacks on Kelly have been especially notable.
The Trump-Kelly beef goes back to the campaign's very first debate, in August. Kelly pushed Trump on his previous statements about women. "You've called women you don't like fat pigs, dogs, slobs and disgusting animals," she said. "Does that sound to you like the temperament of a man we should elect as president?"
So how will Trump respond when Kelly asks him a tough question tonight? Notably, he's stayed away from a confrontation with the network on the eve of this debate.
Will Cruz Focus On Trump Or The Field?
Cruz, Rubio and Kasich each is making the argument that he alone is best positioned to take on Trump in a one-on-one contest. But Kasich hasn't won anything, and Rubio didn't get on the board until Tuesday night, when he carried the Minnesota caucuses.
Last week Cruz trained his fire on Trump. The question for the senator — who won in his home state of Texas, as well as in Oklahoma and Alaska on Tuesday — is whether he keeps that up, or tries to argue that neither Rubio nor Kasich still belongs in the race.
Not Ben Carson
Because he won't be on the stage. On Wednesday, Carson signaled the end of his presidential campaign, saying in a statement, "I do not see a political path forward in light of last evening's Super Tuesday primary results." While Carson hasn't officially ended his campaign, he said he won't attend the debate.
At one point in the race, Carson had stood near center stage as a top-polling candidate. But he faded in November and December, and finished a distant fourth in the Iowa caucuses. Carson stayed in the race, though he had been less and less of a factor in debates.
Last week in Houston, Carson was so frustrated at the lack of questions he was receiving that he begged his opponents, "Can somebody attack me, please?" so that he'd be given an opportunity to respond.