Health research generates knowledge that can be utilized to improve health system performance and, ultimately, health and health equity. We propose a conceptual framework for health research systems (HRSs) that defines their boundaries, components, goals, and functions. The framework adopts a systems perspective towards HRSs and serves as a foundation for constructing a practical approach to describe and analyse HRSs. The analysis of HRSs should, in turn, provide a better understanding of how research contributes to gains in health and health equity. In this framework, the intrinsic goals of the HRS are the advancement of scientific knowledge and the utilization of knowledge to improve health and health equity. Its four principal functions are stewardship, financing, creating and sustaining resources, and producing and using research. The framework, as it is applied in consultation with countries, will provide countries and donor agencies with relevant inputs to policies and strategies for strengthening HRSs and using knowledge for better health.