He sought the Republican nomination in the [[2008 Presidential Election]]. Wisconsin is one of just a few states that is "in play" and can be won by the [[Democrat]]ic or Republican nominee. Thompson was attractive to Republicans because he would likely have won his home state of Wisconsin, and that would have enabled the Republicans to capture the White House without winning Ohio, which has become more Democratic since the Republicans carried that state in the [[United States presidential election of 2004]].
After finishing in sixth place in the [[Iowa Straw Poll]] he withdrew from the race.<ref>[httphttps://www.foxnews.com/story/0,2933,293012,00.html Thompson withdraws from Presidential race]</ref> A few months later he endorsed former Mayor of New York City, [[Rudy Guiliani]].
After Giuliani had withdrawn and endorsed Senator McCain, Tommy Thompson also endorsed him. Thompson said, "Today, I am proud to announce my endorsement of John McCain for president, John McCain has a lifetime of service to our country, and he is the leader best prepared to serve as commander in chief from day one. His conservative record and personal leadership qualities give us the best chance of defeating the Democrats in November." <ref>http://republicancandidates.blogspot.com/2008/02/governor-tommy-thompson-endorses-john.html</ref>
On April 15, 2009, Thompson announced he would not be running for US Senate against [[Russ Feingold]], ending speculation that he would run.<ref>httphttps://www.foxnews.com/politics/2010/04/15/tommy-thompson-opts-senate-bid/</ref> Thompson was considered by many to be the most likely to defeat Feingold and win the seat for the Republicans. Conservative [[Ron Johnson]] defeated Feingold in the election.
Thompson ran for the US Senate seat of retiring Democrat incumbent [[Herb Kohl]] in the 2012 elections. Thompson won the Republican primary but was defeated by Democrat [[U.S. Representative]] [[Tammy Baldwin]].