That, in turn, will shape the fate of President Barack Obama's agenda for the rest of his term. And everything else that Congress wants to do, or stop from getting done.
Republicans need to gain six seats to win back the Senate majority they lost in 2006. Their odds are good, but it's not a slam dunk.
Polls and pundits alike see about 10 Democratic seats that could switch to the GOP. Democrats could flip a GOP seat, too, or perhaps as many as three if they have what passes for a good night.
Voters will also pick a new House of Representatives, choose governors in three dozen states and decide more than 100 ballot measures.
A rundown of what's at stake on Election Day:
Democrats enter the night with a 53-45 Senate majority, and they usually have the support of two independents.
On Tuesday, 36 seats are being contested. Senators serve six-year terms, meaning those elected Tuesday will serve through the next president's first term.
Where will change come?
The GOP's chances are strong of replacing retiring Democratic senators in West Virginia, Montana and South Dakota. Iowa is another possibility, too.
Republican are looking to flip seats in Arkansas, North Carolina, Colorado, New Hampshire, Alaska and Louisiana. There could be GOP losses in Georgia, Kentucky and Kansas.
Republicans aren't expected to win them all, but they don't need them all, either, to make Kentucky's Mitch McConnell the next Senate majority leader - as long as he wins re-election.
IN THE PEOPLE'S HOUSE
Republicans now hold a 234-201 majority in the House. Every election puts all 435 House seats in play. No one doubts the GOP will keep control of that chamber; the question is how many seats they'll gain.
Some two dozen Democrats, along with four Republicans, are seen as vulnerable. If Republicans defeat the most endangered Democratic incumbents and win open seats in North Carolina, Utah and New York, they might end the night with as many as 246 seats, the most for the party since World War II.
AT THE STATEHOUSE
The GOP is defending 22 governor's seats, Democrats 14.
Many of the nation's incumbent state CEOs are vulnerable, more so than usual. A half-dozen Republican governors who swept into office, some with tea party support, in 2010 are struggling to hang onto office.
They include GOP Gov. Sam Brownback in solidly Republican Kansas and Wisconsin Gov. Scott Walker, who is on the ballot for the third time in four years.
Brownback achieved the conservative dream in his first term - big tax and spending cuts. But the effect on the state's budget led many Republicans there to defect, and they support the challenge of Democrat Paul Davis, the state House minority leader.
Walker's chances as a candidate for the 2016 GOP presidential nomination rest on whether he survives a challenge Tuesday from Democrat Mary Burke. Democrats and their labor allies salivate at the prospect of defeating the governor who effectively ended collective bargaining for most public workers in the state after his election in 2010, then survived a recall election.
Several Democrats entered the day struggling to win election, too, most notably in reliably blue New England.
Topping that list is Martha Coakley, who ought to be a shoo-in as a Democrat in Massachusetts. But the state's attorney general, who also lost a bid for Senate in 2010, could fall to Republican Charlie Baker.
This was the first election since both parties fully plunged in to the new world of campaign finance created by Supreme Court decisions that loosened controls on who can spend what and how.
The results were most obvious on TV, which did not lack for political ads in the past. This campaign season in North Carolina: more than 100,000 political ads on TV. Georgia: about 65,000. Kentucky: about 80,000.
Bert Cole, 74, of Jonesboro, Arkansas, couldn't protect himself from the visuals but he did turn the sound off. "I just hit the mute button and let them do their talking."
North Carolina featured the most expensive Senate race in the nation, with more than $108 million spent trying to shape the outcome of Democratic Sen. Kay Hagan's re-election bid against Republican state House Speaker Thom Tillis. Most of the money was from outside groups. Polls suggested the contest was in a tie.
MORE RACES TO WATCH
Like Walker and Brownback, GOP governors Tom Corbett in Pennsylvania, Rick Scott in Florida, Paul LePage in Maine and Rick Snyder in Michigan won with tea party support in 2010 and are standing for re-election for the first time.
In Connecticut, Democratic Gov. Dannel Malloy and Republican Thomas Foley are in rematch of their 2010 race, which Malloy won by fewer than 6,500 votes.
In Kansas, independent Greg Orman could become the kingmaker of the Senate if he defeats Republican Sen. Pat Roberts. Orman could align himself with either party, possibly determining which of them controls the chamber.
In Kentucky: Republican Mitch McConnell vs. Democrat Alison Lundergan Grimes. The Senate GOP leader survived a primary challenge from the right, and a Grimes victory would be a huge upset.
In New Hampshire: Democrat Jeanne Shaheen vs. Republican Scott Brown. Brown, a former senator from Massachusetts, seeks a comeback, this time from across the state line.
In Colorado: Democratic Sen. Mark Udall and Republican Rep. Cory Gardner are in a fierce race, as are Democratic Gov. John Hickenlooper and Republican Bob Beauprez.
ALSO ON THE BALLOT
Among nearly 150 ballot measures being decided Tuesday: legalization of recreational marijuana use in Alaska, Washington, D.C., and Oregon. Anti-abortion measures in Colorado, North Dakota and Tennessee. Labeling requirements for certain genetically modified foods in Colorado and Oregon.