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Abstract Background The interface between research and policymaking in low-income countries is highly complex. The ability of health systems research to influence policy processes in such settings face numerous challenges. Successful analysis of the research-policy interface in these settings requires understanding of contextual factors as well as key influences on the interface. Future Health Systems (FHS): Innovations for Equity is a consortium conducting research in six countries in Asia and Africa. One of the three cross-country research themes of the consortium is analysis of the relationship between research (evidence) and policy making, especially their impact on the poor; insights gained in the initial conceptual phase of FHS activities can inform the global knowledge pool on this subject. Discussion This paper provides a review of the research-policy interface in low-income countries and proposes a conceptual framework, followed by directions for empirical approaches. First, four developmental perspectives are considered: social institutional factors; virtual versus grassroots realities; science-society relationships; and construction of social arrangements. Building on these developmental perspectives three research-policy interface entry points are identified: 1. Recognizing policy as complex processes; 2. Engaging key stakeholders: decision-makers, providers, scientists, and communities; and 3. Enhancing accountability. A conceptual framework with three entry points to the research-policy interface – policy processes; stakeholder interests, values, and power; and accountability – within a context provided by four developmental perspectives is proposed. Potential empirical approaches to the research-policy interface are then reviewed. Finally, the value of such innovative empirical analysis is considered. Conclusion The purpose of this paper is to provide the background, conceptual framework, and key research directions for empirical activities focused on the research-policy interface in low income settings. The interface can be strengthened through such analysis leading to potential improvements in population health in low-income settings. Health system development cognizant of the myriad factors at the research-policy interface can form the basis for innovative future health systems. more...