BACKGROUND: Globally, the response to climate change is gradually gaining momentum as the impacts of climate change unfold. In South Africa, it is increasingly apparent that delays in responding to climate change over the past decades have jeopardized human life and livelihoods. While slow progress with mitigation, especially in the energy sector, has garnered much attention, focus is now shifting to developing plans and systems to adapt to the impacts of climate change. METHODS: We applied systematic review methods to assess progress with climate change adaptation in the health sector in South Africa. This case study provides useful lessons which could be applied in other countries in the African region, or globally. We reviewed the literature indexed in PubMed and Web of Science, together with relevant grey literature. We included articles describing adaptation interventions to reduce the impact of climate change on health in South Africa. All study designs were eligible. Data from included articles and grey literature were summed thematically. RESULTS: Of the 820 publications screened, 21 were included, together with an additional xx papers. Very few studies presented findings of an intervention or used high-quality research designs. Several policy frameworks for climate change have been developed at national and local government levels. These, however, pay little attention to health concerns and the specific needs of vulnerable groups. Systems for forecasting extreme weather, and tracking malaria and other infections appear well established. Yet, there is little evidence about the country's preparedness for extreme weather events, or the ability of the already strained health system to respond to these events. Seemingly, few adaptation measures have taken place in occupational and other settings. To date, little attention has been given to climate change in training curricula for health workers. CONCLUSIONS: Overall, the volume and quality of research is disappointing, and disproportionate to the threat posed by climate change in South Africa. This is surprising given that the requisite expertise for policy advocacy, identifying effective interventions and implementing systems-based approaches rests within the health sector. More effective use of data, a traditional strength of health professionals, could support adaptation and promote accountability of the state. With increased health-sector leadership, climate change could be reframed as predominately a health issue, one necessitating an urgent, adequately-resourced response. Such a shift in South Africa, but also beyond the country, may play a key role in accelerating climate change adaptation and mitigation.