But those two races show the mixed success DeMint's strategy can bring. Rubio has become a rising star in the Senate and for conservatives. But O'Donnell lost her bid in the general election and Republicans lost the opportunity to gain that seat in the senate.
Rubio offered a video message after learning that DeMint was leaving the senate. "Jim DeMint is one of the main reasons I'm in the U.S. Senate," said Rubio, who added he is excited that DeMint will continue to "lead the limited government free enterprise movement from outside the Capitol."
"One of the most rewarding things I've done in the Senate is work with the grassroots to help elect a new generation of leaders who have the courage to fight for the principles of freedom that make this country so great," DeMint said. "I'm confident these senators will continue the legacy of conservative leaders before them."
That's a legacy that even Graham, who could well face a primary from a more conservative republican in 2014, can agree with.
"What he's done over the last four years to build a conservative movement, to get people involved in politics, like Marco Rubio, who Jim helped early on in his primary I just think is going to be a great legacy," said Graham.
Before Congress, DeMint owned an advertising and market research firm. Gov. Nikki Haley, a Republican, will appoint a replacement for DeMint until the next regular statewide election.
Regarding Haley's appointment of a replacement for DeMint, one knowledgeable South Carolina Republican source points to Congressman Tim Scott, who represents the state's 1st Congressional district.
"Tim Scott is the undisputed favorite -- and probably preferred by Jim DeMint," said the South Carolina Republican. "It would be historic for an Indian American governor from the Deep South to appoint an African American to the U.S. Senate. I think it's highly unlikely she would appoint a placeholder. There are too many critical votes coming in the next 24 months. Scott and DeMint are lock step on the issues."
Scott thanks DeMint for his service in his own statement Thursday.
"Looking forward, Governor Haley will now appoint a new Senator, and I know she will make the right choice both for South Carolina and the nation," he said.
The other option for Haley is to appoint someone who does not have aspirations on higher office - a placeholder who would step aside for the special election, allowing Haley and others an opportunity to pursue the seat.