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The Alliance for Health Policy and Systems Research was established in 1999 and is hosted as an international partnership by the World Health Organization (WHO). The Alliance emerged from recommendations of the 1996 WHO Ad Hoc Committee on Health Research, which recognised the role of research in strengthening health policies and the overall development of health systems. Work towards the Alliance’s mission – to promote the generation and use of health policy and systems research (HPSR) as a means to strengthen health systems in low- and middle-income countries – historically focused on three areas: generation of policy and systems knowledge, promotion of its use in decision making to improve the performance of health systems, and strengthening researchers’ and decision makers’ capacity to engage in these efforts. Now, after nearly 20 years of learning and accomplishments, the Alliance is launching new strategic objectives to reflect a changed context, and new challenges and opportunities. Over the coming years, the Alliance plans to provide a unique forum for the HPSR community; support institutional capacity to conduct and use HPSR; stimulate the generation of knowledge and innovations to nurture learning and resilience in health systems; and increase demand for, and use of, knowledge for strengthening health systems.