This chapter explores Isaac Mayer Wise’s interest in politics. This interest raises the question whether at any time he considered making politics his career. As the chapter shows, Wise has been involved in politics and with politicians since his entry into the United States, during the Civil War years, and the years following. At a time of Republican domination (he wrote his Reminiscences in 1874–1875), Wise may have been harking back to a ‘might have been’. His 1858 foray into politics, like his candidature for a state senatorship in 1863, was directed against the Republicans. It is evident, moreover, that Wise’s action in 1858 reached out to something larger than local Cincinnati politics.