Heat and heat waves are projected to increase in severity and frequency with increasing global mean temperatures. Studies in urban areas show an association between increases in mortality and increases in heat, measured by maximum or minimum temperature, heat index, and sometimes, other weather conditions. Health effects associated with exposure to extreme and prolonged heat appear to be related to environmental temperatures above those to which the population is accustomed. Models of weather-mortality relationships indicate that populations in northeastern and midwestern U.S. cities are likely to experience the greatest number of illnesses and deaths in response to changes in summer temperature. Physiologic and behavioral adaptations may reduce morbidity and mortality. Within heat-sensitive regions, urban populations are the most vulnerable to adverse heat-related health outcomes. The elderly, young children, the poor, and people who are bedridden or are on certain medications are at particular risk. Heat-related illnesses and deaths are largely preventable through behavioral adaptations, including the use of air conditioning and increased fluid intake. Overall death rates are higher in winter than in summer, and it is possible that milder winters could reduce deaths in winter months. However, the relationship between winter weather and mortality is difficult to interpret. Other adaptation measures include heat emergency plans, warning systems, and illness management plans. Research is needed to identify critical weather parameters, the associations between heat and nonfatal illnesses, the evaluation of implemented heat response plans, and the effectiveness of urban design in reducing heat retention.