Dengue hemorrhagic fever (DHF) is an acute, potentially life-threatening, capillary leak syndrome caused by the dengue viruses, a group of four antigenically related flaviviruses designated serotypes 1 through 4. First recognized in Southeast Asia in the 1950s, DHF has become a significant public health problem in many countries in tropical and subtropical areas of Asia, the Pacific Rim, and the Americas. In contrast, classical dengue fever, an acute, self-limited febrile illness often called “breakbone fever,” was well recognized before the year 1800. How the same viruses can produce such disparate clinical outcomes has been an area of intense study.