Since cocaine was first synthetized in the late nineteenth century, its licit and illicit flows have been marked by sharp power imbalances between producers and consumers of the substance, and across links of the supply chain. Due to the concentration of production in a few countries, and its tight connection to the geopolitical relation between US and Latin America, the regulation, criminalization, and policing of cocaine flows has been heavily dictated by the United States. International power imbalances have also made the illegal cocaine market one of the most profitable and violent drug markets, and the subject of highly militarized counternarcotic policies. Yet the prevalent view of cocaine markets as the most violent and profitable, and a focus on US influence, often hides domestic struggles around race, class, and political power, and connections with state building and development. The beginning of the twenty-first century marked an expansion of cocaine supply chains, as use and transit routes extended to more countries, potentially altering the traditional power configuration of cocaine smuggling. This chapter revisits the implications of multiple power imbalances, their interaction with domestic politics, and the extent to which changes in the supply chain can alter the politics of cocaine smuggling.