The Illinois senator is seeking his fifth term, but he is facing two main opponents in the 2020 election.
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Former Lake County Sheriff Mark Curran, a Republican, and humanitarian Willie Wilson, running as an independent, both say it's time for a change.
Illinois Election 2020: Meet the Candidates
"He's done nothing for Illinois. He's left Illinois behind and that's why the Tribune endorsed me," Curran said.
"He's the second most powerful Democrat in the United States Senate, and look how many jobs are left in Illinois and look how many people have lost all businesses," Wilson said.
Durbin contends it's his experience that Illinois needs now more than ever.
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"Having served in the Senate and the House of Representatives, I'm in a better position to help this state, help this city through one of the most difficult times we've had in the history of this country," Durbin countered.
Wilson, a wealthy businessman who also previously ran for both Chicago Mayor and President, said he has given away $18 million worth of masks during the pandemic.
"I'm not a career politician. I'm not looking for a paycheck," Wilson said
Curran, a longtime Democrat turned Republican, is hoping to pull off the upset and believes Wilson will draw votes from Durbin.
"I think this first issue is the economy Craig, and I'm fighting for the economy and fighting for the middle class one," Curran said.
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Durbin played a high profile role in the confirmation hearing of Judge Amy Coney Barrett, putting health care front and center as a key issue in his campaign.
"It starts with health care, and I agree with the American people and the people of this state; we've got to have good quality, accessible, affordable health care," Durbin said.
President Donald Trump is also a factor in the race for Illinois Senate.
The way Trump has energized Democratic voters could benefit Durbin. Curran also acknowledges the president could hurt him north of Interstate-80, and Wilson shrugged it off saying he's not running against Trump.