Despite myriad programs aimed at increasing access to essential medicines in the developing world, the global drug gap persists. This paper focuses on the major legal and political constraints preventing implementation of coordinated global policy solutions – particularly, the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) and bilateral and regional free trade agreements. We argue that several policy and research routes should be taken to mitigate the restrictive impact of TRIPS and TRIPS-plus rules, including greater use of TRIPS flexibilities, advancement of human rights, and an ethical framework for essential medicines distribution, and a broader campaign that debates the legitimacy of TRIPS and TRIPS-plus standards themselves.