BACKGROUND: We provide a historical analysis of the evolution of the field of health policy and systems research (HPSR) since 1996. In the mid-1990s, three main challenges affected HPSR, namely (1) fragmentation and lack of a single agreed definition of the field; (2) ongoing dominance of biomedical and clinical research; and (3) lack of demand for HPSR. Cross-cutting all these challenges was the problem of relatively limited capacity to undertake high quality HPSR. Our discussion analyses how these problems were addressed so as to facilitate growth and enhanced recognition of the field. DISCUSSION: HPSR has benefitted significantly from increased recognition of the importance of strong health systems to health outcomes, particularly those linked to the Millennium Development Goals. In addition to this, some of the challenges described above have been addressed through (1) sustained advocacy for the importance of HPSR, (2) efforts to clarify the content and focus of the field, and (3) growing appreciation of and efforts to engage health practitioners and policy-makers in HPSR. While advocacy for the field of HPSR was initially fragmented, since the late 1990s there has been a consistent flow of focusing events and publications that have served to enhance the profile and understanding of the field. There have also been multiple efforts to establish greater coherence within the field, for example, interrogating the distinctions between health services research and health systems research, and how critical the "P" for policy is to HPSR. Finally, HPSR has developed at the same time as growing interest in evidence-informed policy and, more recently, implementation science, which have served to underscore the relevance and utility of HPSR to policy- and decision-makers. CONCLUSIONS: During the past two decades, the field of HPSR has developed significantly, leading to enhanced clarity about its purpose, activity levels and utility. Several challenges remain that will need to be addressed in the decades ahead.