For many sub-Saharan African countries, a National Health Research System (NHRS) exists more in theory than in reality, with the health system itself receiving the majority of investments. However, this lack of attention to NHRS development can, in fact, frustrate health systems in achieving their desired goals. In this case study, we discuss the ongoing development of Zambia's NHRS. We reflect on our experience in the ongoing consultative development of Zambia's NHRS and offer this reflection and process documentation to those engaged in similar initiatives in other settings. We argue that three streams of concurrent activity are critical in developing an NHRS in a resource-constrained setting: developing a legislative framework to determine and define the system's boundaries and the roles all actors will play within it; creating or strengthening an institution capable of providing coordination, management and guidance to the system; and focusing on networking among institutions and individuals to harmonize, unify and strengthen the overall capacities of the research community.