Health policy and systems research (HPSR) has changed considerably over the last 20 years, but its main purpose remains to inform and influence health policies and systems. Whereas goals that underpin health systems have endured – such as a focus on health equity – contexts and priorities change, research methods progress, and health organisations continue to learn and adapt, in part by using HPSR. For HPSR to remain relevant, its practitioners need to re-think how health systems are conceptualised, to keep up with rapid changes in how we diagnose and manage disease and use information, and consider factors affecting people’s health that go well beyond healthcare systems. The Sustainable Development Goals (SDGs) represent a shifting paradigm in human development by seeking convergence across sectors. They also offer an opportunity for HPSR to play a larger role, given its pioneering work on applying systems thinking to health, its focus on health equity, and the strength of its multi-disciplinary approaches that make it a good fit for the SDG era.