Meanwhile, for chief rival Bernie Sanders, the debate is a chance to reach a broader audience after months of appealing to the party’s most liberal voters.
However, unlike recent Republican debates, today’s Democratic outing is expected to be more substance than slugfest.
Analysts expect a heavy focus on economic issues like income inequality.
The three other, mostly unknown, candidates – former Maryland Governor Martin O’Malley, former Virginia Senator Jim Webb and former Rhode Island Senator Lincoln Chafee – will be seeking a standout moment after months of languishing in the polls.
Vice-President Joe Biden, who is still considering a run for the White House, will loom large despite not actually being on stage.
The debate organizers at CNN have set aside a lectern just on the off-chance Joe Biden decides to enter the fray at the last minute. The debate is set to start at 17:30 local time.
Hillary Clinton – long seen as the presumptive front-runner – has seen her support wane amid questions about her trustworthiness.
She has been criticized for using a private email account when she served as secretary of state, a move she now calls a mistake.
Some Republicans say Hillary Clinton put classified information at risk by using the private account – a charge she denies.
On October 22, Hillary Clinton will go before a Congressional panel investigating a 2012 attack on the US consulate in Benghazi, Libya. Four Americans – including the US ambassador to Libya, Chris Stevens, died in the attack.
Critics say Hillary Clinton could have done more as secretary of state to ensure their security.
Her performance in both Tuesday’s debate and the coming hearing are being closely watched as her campaign enters a key phase.
Analysts say Hillary Clinotn needs to shake off perceptions that she is too stiff and overly political by delivering spontaneity and more personal warmth.
BernieSanders, a Vermont Senator who calls himself a democratic socialist, has drawn record crowds in recent months with his message of increased economic fairness for the working class.
He is leading in early voting states of New Hampshire and Iowa and has defied expectations, raising large amounts of money from thousands of small donors.
However, Hillary Clinton maintains a substantial lead in many Southern states like South Carolina and swing states like Nevada, where today’s debate will be held.
Bernie Sanders has resonated with the party’s affluent white voters but has yet to make inroads with African Americans and Latinos – key Democratic constituencies.
Hillary Clinton and Bernie Sanders have mostly avoided direct criticism of each other in contrast to the raucous Republican field.
However, even if the candidates themselves practice restraint, Republican frontrunner Donald Trump promises to provide live commentary on Twitter.
The Democratic debates are between all major candidates running for President in 2016.
The Democratic National Committee has announced six sanctioned debates which will begin on October 13, 2015, in Las Vegas.
The second Democratic debate will take place on November 14 in Des Moines, Iowa.
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