The MRC/Wits Developmental Pathways for Health Research Unit (DPHRU) is situated in the South African Medical Research Council (SAMRC) as an extramural research unit based at the University of the Witwatersrand. At Wits, DPHRU forms part of the Department of Paediatrics and Child Health in the School of Clinical Medicine of the Faculty of Health Sciences. Addressing national priorities of increasing life expectancy, decreasing maternal and child mortality and strengthening health system effectiveness, DPHRU forms a unique research platform with substantial infrastructure and equipment, extensive longitudinal data from the Birth to Twenty Plus cohort, and well-established links with urban and rural South African communities. Specifically, DPHRU investigates genetic, physiological, psycho-social, and lifestyle determinants of growth and development, obesity and risk of cardiometabolic disease, and healthy ageing through innovative multi-disciplinary methodologies across the life-course. DPHRU draws upon a conceptual framework that sees health in adult life as a product of a multi-generational process that can be affected adversely by shocks or deprivation, as well as enhanced by the existence of protective factors or appropriate interventions in critical periods. Insight into the converging complexity of environmental and social factors across the lifespan in South Africa is critical for understanding the pathways to the development of ill-health, engaging in effective advocacy, and leading the development of successful interventions. DPHRU is well positioned to provide scientific and local formative and intervention research in the area of developmental origins of health which will complement the science of existing research entities tackling metabolic disease, health and wellbeing in South Africa.