Each year in the United States, approximately 400 deaths are attributed to excessive natural heat; these deaths are preventable. This report describes heat-related deaths in Missouri, New Mexico, Oklahoma, and Texas when elevated temperatures were recorded for several consecutive days during July-August 2001; summarizes heat-related deaths in the United States during 1979-1999; and presents risk factors and preventive measures associated with heat-related illness and death, especially in susceptible populations.