In this special issue of HAHR two archival historians introduce a new drug history for the Americas. They argue that the fetishization of drugs by prohibitionists and enthusiasts alike has been no accident. Whether due to the resemblance between drug-induced and spiritually inspired ecstasy, or the way that drugs can undermine the razón on which Western civilization has supposedly hinged, or their life-and-death medicinal implications, drugs have been closely tied to fundamental themes and developments throughout Latin American history. These ideas are offered in three parts. First, the editors offer a long-term periodization of drugs in Latin America that frames the big picture and problematizes present distinctions between licit and illicit drugs. Second, they propose a brief set of explicit suggestions on the methodological possibilities of drug history. Third, they present three new essays, focused specifically on the tumultuous long 1960s in Argentina, Colombia, and Mexico, that exemplify how drugs can open new frontiers in the historical study of Latin America.