Universal health coverage has recently become a top item on the global health agenda pressed by multilateral and donor organizations, as disenchantment grows with vertical, disease-specific health programs. This increasing focus on universal health coverage has brought renewed attention to the role of domestic politics and the interaction between domestic and international relations in the health reform process. This article proposes a theory-based framework for analyzing the politics of health reform for universal health coverage, according to four stages in the policy cycle (agenda setting, design, adoption, and implementation) and four variables that affect reform (interests, institutions, ideas, and ideology). This framework can assist global health policy researchers, multilateral organization officials, and national policy makers in navigating the complex political waters of health reforms aimed at achieving universal health coverage. To derive the framework, we critically review the theoretical and applied literature on health policy reform in developing countries and illustrate the framework with examples of health reforms moving toward universal coverage in low- and middle-income countries. We offer a series of lessons stemming from these experiences to date.