Global climate change is projected to increase the frequency and duration of periods of extremely high temperatures. Both the general populace and public health authorities often underestimate the impact of high temperatures on human health. To highlight the vulnerable populations and illustrate approaches to minimization of health impacts of extreme heat, the authors reviewed the studies of heat-related morbidity and mortality for high-risk populations in the U.S. and Europe from 1958 to 2012. Heat exposure not only can cause heat exhaustion and heat stroke but also can exacerbate a wide range of medical conditions.