Health workers are central to people-centred health systems, resilient economies and sustainable development. Given the rising importance of the health workforce, changing human resource for health (HRH) policy and practice and recent health policy and systems research (HPSR) advances, it is critical to reassess and reinvigorate the science behind HRH as part of health systems strengthening and social development more broadly. Building on the recently published Health Policy and Systems Research Reader on Human Resources for Health (the Reader), this commentary reflects on the added value of HPSR underpinning HRH. HPSR does so by strengthening the multi-disciplinary base and rigour of HRH research by (1) valuing diverse research inferences and (2) deepening research enquiry and quality. It also anchors the relevance of HRH research for HRH policy and practice by (3) broadening conceptual boundaries and (4) strengthening policy engagement. Most importantly, HPSR enables us to transform HRH from being faceless numbers or units of health producers to the heart and soul of health systems and vital change agents in our communities and societies. Health workers' identities and motivation, daily routines and negotiations, and training and working environments are at the centre of successes and failures of health interventions, health system functioning and broader social development. Further, in an increasingly complex globalised economy, the expansion of the health sector as an arena for employment and the liberalisation of labour markets has contributed to the unprecedented movement of health workers, many or most of whom are women, not only between public and private health sectors, but also across borders. Yet, these political, human development and labour market realities are often set aside or elided altogether. Health workers' lives and livelihoods, their contributions and commitments, and their individual and collective agency are ignored. The science of HRH, offering new discoveries and deeper understanding of how universal health coverage and the Sustainable Development Goals are dependent on millions of health workers globally, has the potential to overcome this outdated and ineffective orthodoxy.