But the spotlight is largely on two: former Secretary of State Hillary Clinton and Vermont Sen. Bernie Sanders.
The former secretary of state needs to remind viewers of the debate sponsored by CNN and Facebook about why she began the year as the overwhelming front-runner and is best able to take the torch from President Barack Obama.
Sanders has the opportunity to prove to millions of voters why a 74-year-old self-described democratic socialist can take on both Clinton and Republicans.
There's also a lot at stake for the three lesser known underdogs, particularly former Maryland Gov. Martin O'Malley, whose stalled campaigns could benefit from an "all in" performance Tuesday.
Here are CNN's six things to watch in Tuesday night's debate:
Can Clinton flip-flop gracefully?
Hillary Clinton will have to answer for the original sin of politics: flip-flopping.
Clinton came out against the Trans Pacific Partnership last week, when as secretary of state she heralded the agreement as the "gold standard" of trade deals. Her critics quickly accused her of shifting positions for the sake of political expediency in both appealing to liberals and creating distance between her and Barack Obama.
"Wow, that's a reversal," O'Malley, a TPP opponent, said last week. "I can tell you that I didn't have one opinion eight months ago and switch that opinion on the eve of debates."
Clinton has also been accused of doing a course reversal on issues important to the Democratic base, like same-sex marriage and whether she supports allowing undocumented people to obtain driver's licenses. She also only recently opposed the Keystone XL pipeline, after months of dodging the question.
"The greatest opportunity for these other candidates is going to be to go after her on shifting positions, mostly recently on the TPP trade deal," Dan Pfeiffer, a former senior adviser to Obama, said on CNN Monday.
The emails: Will anyone go there?
Clinton has battled, unsuccessfully for months, to overcome the political storm over her private email server.
The attacks have been led by Republicans while Democrats have mostly averted their gaze, hoping it would go away.
It's a tricky issue for a rival candidate to bring up -- they could risk harming their own support among Democrats by raising the divisive issue. But it's still possible that Clinton's rivals -- perhaps Webb or O'Malley -- will gingerly point to the issue on Tuesday as a way of suggesting that she abhors transparency and scrutiny.
"She needs to answer the email questions with transparency and openly," Patti Solis Doyle, Clinton's 2008 campaign manager, said on CNN Monday. She added that Clinton's biggest challenge is to avoid getting "riled up" if put on the defensive.
Clinton's campaign has seized on comments by GOP House Majority Leader Kevin McCarthy that the congressional Benghazi committee was created to hurt her politically, as well as criticisms of the panel by a conservative former staffer.
Donald Trump: Democrats' favorite punching bag?
If Democrats don't attack Clinton, who will they hit? Republicans. Especially Trump, the GOP front-runner whose unorthodox campaign has dominated the 2016 narrative so far.
Look for the five Democrats on stage to go after Republicans from the start. The wealthy New York real estate developer presents an alluring target, and the more they can tie Trump to the overall Republican Party, the better.
The Democratic Party has used some of Trump's unfiltered remarks on everything from immigration to women to paint the GOP with a broad brush and label the party as exclusive and intolerant.
Feel the Bern
By now, Bernie Sanders is used to being the star at the center of the stage.
He's drawing tens of thousands of supporters to campaign rallies, and he's become a liberal sensation, inspiring the popular slogan "Feel the Bern" among progressive Democrats. He's also giving Clinton a run for her money in early states like Iowa and New Hampshire.
Still, the pressure Tuesday night will be like none the Vermont senator has faced so far in the cycle.
Sanders has decades of experience in public office, but in some ways, he seems like a stylistic misfit for the presidential debate stage based on the campaign he has run thus far. He tends to give long and at times rambling speeches, he has repeatedly said he has no interest in attacking his fellow Democratic rivals, and his aides say he's barely engaged in traditional debate prep in the days leading up to Tuesday.
The added challenge for Sanders will be to win over viewers who are skeptical about whether the senator can rise to the occasion of being a national leader.
Which Clinton shows up?
Clinton has spent months on the defensive, due to the controversy over her private email server and surprised by the strong progressive surge that's powering Sanders to her left.
She's come across as not forthcoming in some interviews, reminding voters of the political obfuscation that at times clouded her husband Bill Clinton's administration in the 1990s. Clinton's poll numbers and approval ratings have dipped as a result.
But she's a known strong debater, and went toe to toe with Barack Obama again and again in 2008. A repeat of those assured, likable performances on Tuesday night could go a long way toward reminding 18 million Democrats why they voted for her in her first presidential primary campaign.
"Hillary Clinton is an excellent debater," said Pfeiffer. "She is excellent, crisp, knows the substance up and down, is very good in the back and forth."
For all her struggles in the race so far, she is still the overwhelming front-runner and faces by far the highest expectations.
Clinton also knows the dangerous potential of debates. Her halting answer about driving licenses for undocumented migrants in the 2008 season was the first crack in a front-running White House campaign that Obama eventually overhauled.
Is this Martin O'Malley's only chance?
O'Malley has spent months berating Democratic leaders for failing to schedule more debates, all as he has struggled to climb above single digits in the polls.
Once seen as a fresh and accomplished new Democratic voice, the former Maryland governor -- partly due to his failure to command much media coverage -- is badly in need of a fresh boost of energy.
He and his other underdog rivals, Jim Webb and Lincoln Chafee, will want to emulate Carly Fiorina. The former Hewlett-Packard CEO used fiery performances in the GOP debates to jump-start a stalled campaign and put herself into the top tier of GOP candidates.
O'Malley, 52, is also by far the youngest person on the stage. Sanders is 74, and was born months before America entered World War II. Most of the rest are baby boomers. Clinton is 67, Jim Webb is 69 and served in the Vietnam War, and Lincoln Chafee is 62.
Unlike the Republican primary, which features candidates spanning generations -- Marco Rubio and Bobby Jindal are just 44 -- the Democratic contest looks like it is for seniors only. The age gap could give O'Malley an edge. And he'll need any advantage he can get.
"The one person who has a great opportunity here is Martin O'Malley," former Mitt Romney adviser Kevin Madden said on CNN Monday. "When you're at 1%, and you're Martin O'Malley, that's very easy. He has nowhere to go but up."
Clarification: This story has been updated to better reflect Clinton's position on immigration policy.