Witherspoon, an orthodontist, is known as an arch-conservative on social and cultural issues, and plans to run a campaign centered on fighting illegal immigration.
But as a first-time candidate, he will face an uphill battle raising his name identification and money against a very well-funded incumbent. Graham has over $4.2 million in his campaign account at the end of the third quarter.
Graham has been criticized by some conservatives for his role in advocating for comprehensive immigration reform legislation, which failed to pass the Senate earlier this year.
The primary is scheduled for June 10, 2008.