Nearly 1500 malaria cases occur each year in the United States; approximately 60% are among U.S. travelers. Despite the availability of sophisticated medical care, malaria-related deaths continue to occur. The authors reviewed all 185 fatal cases between 1963 and 2001 that were reported to the National Malaria Surveillance System: 123 (66.5%) occurred among U.S. travelers, and of these, 114 (92.7%) were attributed to Plasmodium falciparum. Failure to take or adhere to recommended chemoprophylaxis, to promptly seek medical care for post-travel illness, and to promptly diagnose and treat suspected malaria all contributed to fatal outcomes. Health care providers need to take a travel history, obtain a blood film for suspected malaria, and use the 24-hour malaria management advice available through the Centers for Disease Control and Prevention (CDC) Malaria Hotline (770-488-7788) or the CDC Malaria Web site (http://www.cdc.gov/Malaria). Hospitals must maintain intravenous quinidine gluconate on formulary because it is the only drug available to treat severe malaria in the United States.