Almost as soon as Cheney announced her intentions on Tuesday, the National Republican Senatorial Committee made it clear it would be backing Enzi, supporting the incumbent as it traditionally does and noting it would provide back up to Enzi if necessary.
Brian Walsh, former spokesperson for the NRSC and current GOP strategist, said Cheney has to be "very careful" when it comes to criticizing Enzi and using "code words" as she did this week.
"You have to be careful, especially in a small state where everyone knows each other," Walsh said. "Senator Enzi is still well-liked in Wyoming, and in a small state if the vast majority of voters have met and feel like they know him, it becomes much more personal."
Wyoming is the least populous state in the nation with about 576,000 residents. According to the Wyoming Secretary of State's office, as of this month there are 166,643 Republicans and 53,301 Democrats in the state; 36,491 voters are registered as unaffiliated or as Libertarian or Constitution Party members.
Wyoming also allows voters to change their party registration on Election Day, which would allow Democrats to cross over and vote for Enzi, possibly just to be able to vote against a member of the Cheney family.
Cheney, with the help of her famous father, will no doubt be a formidable fundraiser, a potential problem for Enzi who has admitted his weakness raising money. In the three previous races, where he has sailed to victory, he has only spent a total of $4.2 million.
But, in a state so spread out, with such small urban centers, money isn't everything and the University of Wyoming's King warned that blanketing the airwaves runs the risk of alienating voters or "overexposure."
"There is that risk if you become consistently and frequently negative you create in essence a sympathy vote," King said. "You can't go about advertising with a lot of money in Wyoming the same way you would in a lot of states."
Cheney moved to Wyoming last year and has been making the rounds at GOP dinners and fundraisers. Her father was the state's at-large congressman and her family has called the state home for generations, but she has spent most of her adulthood in Washington, D.C., and Northern Virginia. She was clearly hoping with her movements in the state and now with her candidacy that it would be enough to push Enzi into retirement.
But, it doesn't look as if Enzi will go quietly. Thursday he released a statement saying in clear terms that he intends to run for reelection.
"Wyoming people don't like long campaigns," Enzi said foreshadowing what is likely to be a bloody GOP primary fight. "When the time comes, I am confident the people of Wyoming will vote for my results, dedication, legislative experience and hard work for the state."
He also thanked supporters for the "many calls and emails my family and I have received in the last few days."
"So many people are telling us they remain committed to me and will do whatever they can to see that I can continue to faithfully represent them," he wrote, adding that he will "continue to do what is right," which includes treating "others as they expect to be treated."
This story has been updated since it was first posted. Originally it described Strom Thurmond's opponent Elliot Close as a Republican, he was a Democrat.