Climate change is the biggest global health threat of the 21st century. [1] Unprecedented global warming associated with anthropogenic activities has catalysed a 'greenhouse effect' which has led to changes in earth systems [2] that are increasingly deemed irreversible. [3-5] Extreme weather events are predicted to increase (or are already increasing) in severity and frequency. [6] These climatic changes threaten environmental conditions required to support human health and wellbeing, including air that is safe to breathe, water that is available and clean to drink, food that is of nutritional value and shelter from the elements. [7] Associations exist between exposure to high ambient temperatures during a heatwave, for instance, with heat having particularly harmful effects on cardiovascular and respiratory health. [1] The changing availability and compromised quality of water associated with a changing climate may lead to increases in waterrelated diseases such as cholera. [8] Increased droughts, flooding and proliferation of pests are considered the main threats to food security. [9] Extreme weather and climate events can displace and compel people to migrate because of the destruction of their homes (for example by storm surges), rendering the local environmental uninhabitable. [10] In this article, studies conducted by the South African Medical Research Council's (SAMRC) Environment and Health Research Unit were gathered and used to illustrate the range of possible research key areas in the climate, heat and health domain. Using national and international published and grey literature, and tapping into institutional research experiences, an overview of research findings to date, and future research priorities, are presented. Why is South Africa (SA) more vulnerable than many other nations to the ramifications of climate change? Scientific models and projections indicate that southern Africa will be particularly affected by climate change. Local temperatures are expected to increase, on average, by a rate that is double the projected average for the globe. [11,12] SA may also become increasingly prone to lowered precipitation, droughts (such as the episode that gripped the Western Cape in 2017-2018), heatwaves This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.