The South African government has taken several steps in response to climate change and its associated threats to human health. The National Climate Change Response Plan White Paper defines government's vision for effective climate change response and transitioning to a climate-resilient, low-carbon economy. The White Paper identifies potential health challenges for South Africa (SA), including vector- and water-borne diseases and heat stress. The National Climate Change and Health Adaptation Plan (the Plan), prepared by the National Department of Health, expands on these health challenges, raising not only additional ones, but also related socioeconomic risk factors, such as housing and settlements. Community participation was adopted as one of the guiding principles for implementing the Plan, especially as behavioural change is likely to be important for adaptation and coping strategies. Multisectorial co-operation is also imperative, as many of the climate-related health risks involve multiple multidisciplinary stakeholders to implement appropriate interventions. Addressing inequalities and poverty in SA is critical to ensure that the health impacts from climate change are mitigated, particularly as current evidence suggests that the largest health risks are possibly among communities already most impacted by climate-related diseases. More research is needed to determine the impact of climate on health and which communities are the most vulnerable. Tailored monitoring and evaluation systems, linked with climate surveillance, will provide an opportunity to collect health data on key health risks to inform decision-making.