[3][4][5] He chose not to run for reelection to the Senate in 2010;[6] former State Attorney General Kelly Ayotte, also a Republican, was elected to succeed him.

After withdrawing from his nomination to become United States Secretary of Commerce in the presidential administration of Democrat Barack Obama on February 12, 2009, Gregg said he would "probably not" seek reelection in 2010, when his term of office was set to expire.

[18] On November 14, 2008 Gregg was appointed by United States Senate Minority Leader Mitch McConnell to serve on the five-member Congressional Oversight Panel created to oversee the implementation of the Emergency Economic Stabilization Act.

Gregg "stepped aside" on December 1, citing his Senate workload: I regret that due to the impending Senate schedule involving the potential of dealing with an extremely large stimulus package, coupled with the ongoing issues of developing fiscal policy relative to the budget and the continuing economic downturn and my responsibility for foreign operations appropriations, it has become difficult to continue service on the TARP oversight board.

Resolution 83, which according to REP "included only one revenue-raising instruction to Senate appropriations committees, an abuse of the congressional budget process in order to force oil drilling in the Arctic National Wildlife Refuge", and "would perpetuate America's dangerous oil dependence and damage the most scenic, wildlife-rich reserve in the circumpolar north.

The systemic risk today is the Congress of the United States ... we're creating these massive debts which we're passing on to our children ... (the figures) mean we're basically on the path to a banana republic-type of financial situation in this country.

On October 29, 2007, Gregg endorsed Mitt Romney, former Governor of Massachusetts, to be the Republican nominee for President of the United States.

The six accused were: Alberto Gonzales, David Addington, William Haynes, Douglas Feith, Jay Bybee, and John Yoo.

[29] In the Senate, Gregg was the leading Republican negotiator and author of the TARP program, which bailed out financial institutions, while he had a multimillion-dollar investment in Bank of America.

[33] In February 2009, the Associated Press reported that Gregg and his family had profited personally from federal earmarks secured by the senator for the redevelopment of the Pease Air Force Base in Portsmouth, New Hampshire into an industrial park.

[34][35] Gregg has denied any wrongdoing in the matter and claimed that his withdrawal from consideration for the Commerce Secretary was unrelated to the White House's discovery during the vetting process of his involvement in his family's real estate investments in Pease.

"[34][36] Gregg as a member of President Barack Obama's deficit commission defended cutting Social Security by quoting Willie Sutton who, when asked why he robbed banks, replied, "because that's where the money is.

"[37] On February 2, 2009, Politico and CNN reported that Gregg accepted President Obama's offer to be the next United States Secretary of Commerce.

[43] On February 12, 2009, Gregg withdrew his name from consideration for the position of United States Commerce Secretary, citing disagreements with issues surrounding the census and the stimulus bill.

[44] White House Press Secretary Robert Gibbs issued a statement regarding Gregg's withdrawal in which he accused the senator of not following through on his alleged statements of support for Obama's economic agenda made during the vetting process:[45] Senator Gregg reached out to the President and offered his name for Secretary of Commerce.

[46]In February 2009, the Associated Press reported that Gregg and his family had profited personally from federal earmarks secured by the Senator for the redevelopment of the Pease Air Force Base into an industrial park.

[35] Gregg claimed that his withdrawal from consideration for the Commerce Secretary was unrelated to the White House's discovery during the vetting process of his involvement in his family's real estate investments in Pease.