Now Democrats have to decide how to wage that battle without him.
Heading into last year's elections, the Nevada Democrat delighted in repeatedly slamming Charles and David Koch -- using the Senate floor to call them "un-American" and accuse them of "trying to buy America" -- as he flaunted the mega-donors' ties to the GOP. But many of the candidates backed by the Kochs won in 2014, Democrats lost control of the Senate, and Reid will retire at the end of next year.
Setbacks aside, Reid insists he has no regrets about his strategy and doesn't plan to back down during his remaining time on Capitol Hill. In a brief interview recently, he told CNN he will go after the Kochs "as much as I can" before retiring.
But once he's gone, will a new Democratic ringleader take over Reid's mission of casting the Kochs as modern political villains?
Sen. Chuck Schumer, in line to take Reid's job in 2017, declined to comment when asked about the Koch brothers. Senate Minority Whip Dick Durbin said his party shouldn't "ever back away" from scrutinizing the Kochs. But pressed on whether he has any interest in assuming Reid's role of chief antagonist, the senator from Illinois chuckled: "It isn't as though Harry hands the baton off to anyone."
Hillary Clinton, the presumed Democratic presidential front-runner, has yet to mention the Kochs publicly since launching her second White House bid. She has, however, indicated plans to help raise money for a pro-Clinton super PAC that Democrats hope could rival the Kochs' fundraising prowess.
Meanwhile, the Kochs are doubling down.
The billionaire industrialists seem more eager than ever to flex their muscles in 2016, an election cycle that is certain to cement their status as two of the most powerful Republican donors in an era of virtually unlimited outside political spending.
They're currently eying their favorite candidates in the crowded Republican field, have pledged to raise an eye-popping $900 million for the 2016
cycle, and launched an aggressive public relations campaign to revamp Koch Industries' reputation.
Republicans have long declared the strategy of bashing the Kochs a failure.
"I've heard Democrats say it would have been worse without the Koch strategy," said Tim Phillips, president of the Koch brothers-founded Americans for Prosperity.
"What's worse than nine seats? It doesn't get much worse than that," Phillips says, referring to the number of Senate seats the GOP gained in 2014.
Koch Industries spokesman Ken Spain said an anti-Koch campaign in 2016 will only be as successful as it was in the 2014 cycle.
"If politicians or political organizations decide to double down on falsely attacking the reputations of Koch Industries, its shareholders, and 60,000 American employees, it is likely to be as successful as it was in 2014," Spain said in a statement to CNN.
But plenty of Democrats, including top strategists involved in the 2014 election's anti-Koch messaging, insist that the Kochs are not about to be let off the hook.
While most Americans still don't even know who the Koch brothers are, some Democrats argue that tying Republicans to the media-shy billionaires has helped identify the GOP as the party of wealthy people and special interests, an image that has badly wounded candidates over time.
"My view is not that Democrats did too much of it but did too little," Democratic pollster Geoff Garin said.
Rather than ending the Koch attacks, Garin said that Reid's departure after 2016 would simply mean the message will be delivered "by a chorus, rather than a soloist."
Joining that chorus is Vermont Sen. Bernie Sanders, an independent seeking the Democratic nomination for president. Soon after launching his campaign, the populist senator called for
a "political revolution" to take on the "billionaire class," pointing to the Koch brothers as a part of the problem.
But the 2014 cycle revealed just how difficult it is to convince voters that candidates are unfit for office simply because they've benefited from donations from the Kochs.
Part of the problem is that the Kochs never became household names. Even as Democrats ratcheted up their attacks on the two men, half of Americans didn't recognize the names Charles and David Koch, according to a WSJ/NBC poll
in April 2014. Despite the expensive campaign to demonize the businessmen, just 21% of the public had negative feelings toward the Kochs, the poll found.
In West Virginia's 3rd Congressional District, Democrats unleashed a torrent of ads slamming GOP candidate Evan Jenkins and the financial backing he received from the Kochs. Democrats lost their battle there -- Jenkins, a former state senator, defeated longtime Rep. Nick Rahall, 55% to 45%.
Andy Sere, a Republican strategist who advised Jenkins, said the slew of anti-Koch ads in the district ultimately did little to paint Jenkins in a negative light.
"Instead of using our guy's record to prosecute a case against him, they put all their eggs in a flimsy guilt-by-association attack that failed miserably, even in this strongly populist district," Sere said. "There were some ads where they spent 26 seconds talking about the Kochs and four seconds on Jenkins, which was fine by me."
Democrats acknowledge that the Koch strategy proved to be more potent in some races than others. A major takeaway from 2014 was that attacks against the Kochs resonate more deeply if they accuse the brothers and their business of directly hurting local constituents.
"If you talk about the Koch brothers as an amorphous, D.C. big money and politics, it's not a very effective message because people don't see how it affects them in their daily lives," said Eddie Vale, vice president of American Bridge, a Democratic super PAC. "But when you can connect it to people's lives, then it makes a lot more sense."
One model race Democratic strategists point to is Gary Peters' successful bid for the Senate in Michigan.
Peters' campaign and his supporters ran ads that not only criticized the Kochs and their outsize spending in politics but also accused one of their companies of creating pollution in the state. One Democratic Senatorial Campaign Committee ad slammed the Kochs for hurting "seniors and children with asthma."
"It's obviously more effective when you have some sort of tangible issue or some sort of tangible action by the Koch brothers that is inconsistent with their political agenda," Peters said.
If partisan strategists are torn on the effectiveness of the Koch-bashing tactic, some political observers say the core strategy is worrisome. The deeply personal and vitriolic statements and ads have set a dangerous precedent, critics say, by marking two private citizens as political targets -- even if they happen to be among the most wealthy and influential men in U.S. politics.
"I don't think it's really healthy for American politics to essentially have these proxy fights over these wealthy funders," said Bruce Haynes of Purple Strategies, a bipartisan consulting firm. "Folks like the Koch brothers have the money to defend themselves but ... if they didn't have the money to defend themselves and they're attacked by these large organizations like this, it's a very chilling thought."