Two of those – Ohio and Texas – are considered crucial for her campaign to survive, but surveys show Senator Clinton's race against Barack Obama is still too close to call.
Ohio and Texas represent the lion's share of the 370 delegates up for grabs on what has been dubbed Super Tuesday II.
Before the primary and caucus season began in January, Mrs Clinton had double digit leads in the polls in both states.
They contain large numbers of voters of Clinton's political bedrock: working-class men, union members, Hispanic voters and older, Democratic supporters loyal to her husband.
But the momentum generated by the race's overall front-runner Senator Obama, who has won the last 11 contests, has started to lure away some of Mrs Clinton's core supporters, as well as several Super Delegates who previously supported the former First Lady.
Super Delegates are party officials and Democratic party politicians who have a free vote at the party's convention in the summer. They could hold the key to this year's close contest.
Mr Obama's confidence was evident in a television interview with ABC's television show Good Morning America.
“If we do well in Texas and Ohio, I think the math is such where it's going to be hard for her to win the nomination,” he said.
“They'll have to make a decision about how much longer they want to pursue it.”
But various polls still give Mrs Clinton anywhere between a 1% and 12% lead in Ohio. The contest in Texas appears to be much tighter.
Vermont and Rhode Island will also vote – the latter is considered to be the most solidly Democratic state in the union.
If Mrs Clinton loses there, she may not miss its 32 delegates, but it will signal a loss of support among the party's faithful.
The eventual winner will take on John McCain, the Republican Party's presumptive nominee, in November's general election to become leader of the free world.