Dengue is a major global health concern. Its increasing incidence and continued geographical spread make the development of an effective vaccine an international health priority. Dengue is currently present in more than one hundred countries, while up to 3 billion people are estimated to be at risk of infection. In addition, dengue is associated with a substantial economic burden that is particularly severe at the individual family level. Establishing the full human cost and economic impact of dengue remains urgent. The approaches being investigated for vaccine development include the use of live, vectored and killed, and recombinant preparations. Vaccine candidates must provide broad and robust immunity to all four dengue serotypes simultaneously as secondary dengue infections may lead to enhanced disease severity. The design, implementation, and surveillance measures associated with dengue vaccine trials need to be particularly rigorous due to the complexity of the disease and its epidemiology. Therefore, eligible trial sites must satisfy several criteria including documented hyper-endemicity and a known epidemiological history of the circulating serotypes. Epidemiological data from Ratchaburi province in Thailand strongly support this location's suitability for a proof-of-concept efficacy trial of the sanofi pasteur tetravalent dengue vaccine. Accurate disease surveillance and carefully monitored clinical trials will provide essential evidence concerning the efficacy of candidate dengue vaccines, which will hopefully herald a new era in dengue disease prevention.