The association between climate change and the frequency and intensity of extreme heat events is now well established. General circulation models of climate change predict that heatwaves will become more frequent and intense, especially in the higher latitudes, affecting large metropolitan areas that are not well adapted to them. Exposure to extreme heat is already a significant public health problem and the primary cause of weather-related mortality in the U.S. This article reviews major epidemiologic risk factors associated with mortality from extreme heat exposure and discusses future drivers of heat-related mortality, including a warming climate, the urban heat island effect, and an aging population. In addition, it considers critical areas of an effective public health response including heat response plans, the use of remote sensing and GIS methodologies, and the importance of effective communications strategies.