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This article examines two spheres of global governance in which the World Health Organization (WHO) has sought to exercise international leadership — combating “counterfeit” medicines and illicit trade in tobacco products. Medicines and tobacco products lie at polar opposite ends of the health spectrum, and are regulated for vastly different reasons and through different tools and approaches. Nevertheless, attempts to govern counterfeit trade in each of these products raise a host of somewhat similar challenges, involving normative and operational conflicts that cut across the crowded intersection of health protection and promotion, intellectual property protection, and activity to combat transnational organized crime. As negotiations of an illicit trade protocol to the WHO Framework Convention on Tobacco Control enter their final stages, lessons learned from counterfeit medicines governance need to be applied to ensure that the most appropriate governance arrangements are adopted.