Coinfection with Mycobacterium tuberculosis and human immunodeficiency virus (HIV) is responsible for one-third of all deaths due to acquired immunodeficiency syndrome. More than 99% of cases of HIV-M. tuberculosis coinfection occur in the developing world, where limited resources add urgency to the search for effective and affordable therapies. Although antimicrobial agents against each of these infections are available, single agents that have activity against both M. tuberculosis and HIV are uncommon. The activity of nicotinamide has been evaluated in 2 different eras: in anti-M. tuberculosis studies performed during 1945–1961 and in anti-HIV studies performed from 1991 to the present. This review brings together these 2 bodies of inquiry and raises the possibility that, with more study, this small molecule could emerge at the beginning of the 21st century either as a therapeutic agent in itself or as the lead compound for a new class of agents with activity against both M. tuberculosis and HIV.