With over 400,000 deaths attributed to opioid use and addiction since the beginning of the 21st century, what have American policy and practice done in response, and where do we go from here? In this special issue of the Journal of Health Politics, Policy and Law, leading scholars on American politics take up these questions and reveal how the opioid epidemic provides new insights on enduring features of American politics and policy. Key among these features is the persistent power of race in shaping public opinion on the opioid crisis, influencing the development of both punitive and treatment-oriented legislation, and impacting media portrayal of these drugs and the communities they affect. The opioid epidemic also reveals multiple, simultaneous systems failures and the challenge of crafting interventions that work on the frontlines. Articles in this volume reveal how to construct information campaigns more effectively, though producing meaningful frontline service delivery will require structural changes beyond better information.