Here are some of those key races:
Beyond the seven tossups, four states are expected to split evenly between Democrats and Republicans.
In Arizona, incumbent GOP Sen. John McCain appears to be holding a solid lead against Democratic rival Ann Kirkpatrick, with a comfortable 16 point average lead in the polls. Republicans are also holding down ballot support in Ohio, where incumbent Sen. Rob Portman holds a solid lead over Democratic rival Ted Strickland.
Democrats hold solid leads in Illinois and Wisconsin, where victories would take away two seats from GOP incumbents. Illinois Republican Sen. Mark Kirk is trailing Democratic challenger Tammy Duckworth by seven points; in Wisconsin, former Democratic Sen. Russ Feingold is hoping to take back the seat he lost to GOP Sen. Ron Johnson in 2010. Feingold holds a 5.3 percent lead in the polls.
That leaves the seven "tossups" where five of the races are virtual dead heats. Democrats would have to pick up at least two of them to win back Senate control.
Though Indiana has typically been a reliably red state, the retirement of Republican Sen. Dan Coats has given an opening to Democrat Evan Bayh, a former governor and senator who retired in 2011. While the race is expected to be close, Bayh has a slight lead in the polls with less than three weeks left in the campaign.
GOP Sen. Roy Blunt held a comfortable lead through the summer, but his race against Democrat Jason Kander, Missouri's secretary of state, has tightened considerably. The final count is expected to be close.
Once considered a safe Republican seat, incumbent Sen. Richard Burr is in a tough fight against Democrat Deborah Ross, a former state legislator, who briefly led Burr in the polls earlier this month. Burr's campaign has also benefited from Hillary Clinton's aggressive campaign in the state, where she has opened up a slight lead against Trump in the polls.
After deciding to run for re-election following his failed presidential bid, GOP primaries Sen. Marco Rubio has a comfortable lead against former Democratic Congressman Patrick Murphy. But Clinton has opened up a four point lead against Trump in the state, which could create a headwind for Rubio in the final weeks of the campaign.
Clinton's lead against Trump may also help Democratic Gov. Maggie Hassan in her bid to unseat incumbent Republican Sen. Kelly Ayotte, who has struggled to distance herself from Trump after earlier citing him as a role model for children. Polls show the race is in a virtual dead heat.
GOP Rep. Joe Heck is hoping to flip this Senate seat from blue to red, following the retirement of Senate Minority Leader Harry Reid. But Reid's handpicked replacement, Catherine Cortez Masto, is holding a slim lead in the polls after trailing Heck for most of the race. Heck has tried to distance himself from Trump, recently calling on him to quit the presidential race.
This battleground state is another for the Republicans to lose. Incumbent GOP Sen. Pat Toomey has trailed Democratic challenger Katie McGinty, but the latest polls show them tied. Pennsylvania has a split Congressional delegation but has voted for Democrats at the top of the ticket in the last six presidential elections.