[5] Griffith was recruited on a "cold call" to Alabama and established the Huntsville Cancer Treatment Center.[which?][when?]

Griffith also conducted several clinical trials in conjunction with the University of Alabama School of Medicine, and partnered with St. Jude Children's Research Hospital in Memphis, Tennessee.

[citation needed] On March 22, 2008 Griffith announced that he would run for the open seat in the 5th District.

[8] He won the June 2008 Democratic primary election with 90% of the vote, defeating physicist David Maker.

[9] Griffith faced Republican Wayne Parker, an insurance agent from Huntsville, in the November election.

It last supported a Democrat for president in 1984,[10] and George W. Bush and John McCain won the district by wide double-digit margins in 2000, 2004 and, ultimately, 2008.

This came even as McCain (who carried the 5th with 61 percent of the vote) and Alabama Senator Jeff Sessions (whose seat was up for re-election) won every county in the district.

His victory, and that of Bobby Bright in the 2nd District, gave Alabama two white Democratic congressmen for the first time since Glen Browder and Tom Bevill left the House in 1997.

He cited the health care bill as a major reason for his switch, and he had also clashed with the Democrats over fiscal and foreign policy.

During his announcement, he stated: I believe our nation is at a crossroads and I can no longer align myself with a party that continues to pursue legislation that is bad for our country, hurts our economy, and drives us further and further into debt.

[21]The GOP had been courting Griffith since August, when he publicly criticized the Democratic House leadership in the wake of raucous town hall meetings in his district, stating that he wouldn't vote for Nancy Pelosi as Speaker as she is "divisive and polarizing".

Upon Griffith's party switch, he became the first Republican to represent Alabama's 5th district since John Benton Callis, who was elected to a single term (1868-1870) during Reconstruction.

He was successful in obtaining the party's nomination but lost decisively to the incumbent, Robert J. Bentley, in the general election.

[26] During the election, Griffith conducted an interview with radio show host Matt Murphy.

[28] In April 2022, Griffith appeared on The Jeff Poor Show, a radio program, where he criticized Michael Durant, one of Britt's opponents in the election.

He co-founded the Griffith Family Foundation, which awards cash grants to elementary school libraries in northern Alabama.