During the 1920s the Eastern Mediterranean emerged from decades of war, economic crisis, and unprecedented state intervention as the nexus of the global opiate trade. The nascent Turkish Republic became the world’s largest producer of opiates with manufacturers in Istanbul alone refining approximately twelve tons of heroin and morphine annually. These drugs were smuggled through the ports of French Mandate Lebanon and into British-occupied Egypt where they precipitated an opiate epidemic that state authorities estimated to claim nearly four percent of the country’s population. This paper investigates how opiate trafficking produced informal circuits of profit and power that transformed the borders and political systems of the Eastern Mediterranean throughout the early twentieth century. It examines the inner workings of trafficking networks at the height of the trade in the late 1920s and early 1930s, detailing heroin production on the banks of the Bosporus, its transit via passenger steamers calling at the ports of Beirut and Alexandria, and its sale in the cafes and alleyways of Cairo. This work juxtaposes official records from the Turkish, Egyptian, French, and British archives with periodicals, memoirs, and popular sources that narrate the accounts of merchants and traffickers. It demonstrates how smuggling served as a mode of grassroots resistance to increasingly totalizing manifestations of state power from British-imposed austerity in turn of the century Egypt to the statist economic program of interwar Turkey. Such furtive illicit activity helped average people fend off the growing reach of centralizing states, preserve local autonomy, and define their status as citizens within emerging political systems on their own terms. State and popular politics have largely overshadowed this scarcely studied form of everyday resistance. However, this paper contends that illicit trafficking influenced the institutional, socio-economic, and political geography of the Eastern Mediterranean from the ground up.