This chapter provides an overview of the history of drug regulation in the United States in order to better understand how events and processes that occurred in the country at the turn of the twentieth century led to the development of the world’s earliest international drug policy. We investigate the history of cocaine and opiates in the United States and question how and why the drugs came to be subject to controls under American law and criminal justice policy. This chapter concludes with an overview of the historical and political processes through which late nineteenth and early twentieth American drug policymakerspolicymakers and advocates helped to establish the world’s first international drug policy.