In this introduction we briefly review the literature on intellectual property rights and access to medicines, identifying two distinct generations of research. The first generation analyzes the origins of new intellectual property rules, in particular the World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), and the significance of TRIPS to developing countries. The second generation examines national-level experiences, as countries adjust their laws and practices to conform to TRIPS.Based on the insights provided by the articles in the special issue, we contribute to the second generation by considering a pair of overarching sets of issues. First, we highlight the domestic political challenges that affect how countries go about implementing their new obligations under TRIPS. We argue that alliances and coalitions are necessary to underpin the use of policy instruments designed to conform to TRIPS while taking into account local conditions and needs, , and we present insights that allow us to understand why alliances and coalitions are difficult to construct and sustain in this area. Second, we explain why policies that many countries adopt in response to TRIPS often do not generate their desired or intended outcomes. In the last section of the introduction we review the articles that appear in this special issue.