Decisions taken by stakeholders at all levels of health systems can benefit from the use of different types of evidence drawn from heterogeneous research fields – including epidemiology, clinical and basic biomedical research, and health policy and systems research (HPSR). However, out of these diverse forms of evidence, HPSR is relatively underused and under-funded. Challenges associated with the use of HPSR in health systems in low- and middle-income countries (L&MIC) include the lack of opportunity and resources, the need for greater capacity for the generation and use of evidence, and fundamental problems around how the research agenda is framed. Evidence informed decision-making in L&MICs can be improved by better alignment of HPSR with health system needs, institutionalizing the use of HPSR evidence, and strengthening individual capacities to generate and use HPSR evidence. Several global, national and local-level initiatives have helped take strides in these areas, but more work and investments are needed to strengthen the use of appropriate evidence, especially HPSR evidence, in health systems.