Because of the increasing incidence, geographic expansion and economic burden of dengue transmission, dengue poses major challenges to policy makers. A vaccine against dengue is urgently needed, but vaccine development has been hampered by the lack of an appropriate animal model, poor understanding of correlates of successful human immunity, the fear of immune enhancement, and viral interference in tetravalent combinations. The most suitable target epitopes for vaccines, as well as the role of nonstructural proteins remain elusive. The chimeric yellow fever bone-based live attenuated dengue vaccine is furthest in development, but initial efficacy results have been disappointing. Lessons learnt from this failure will affect the design of future trials, and increase the urgency to identify the best epitope and immune correlates. Dengue vaccine introduction will not be the only strategy to combat dengue, but needs to be "packaged" with novel vector control approaches, with community-based interventions to reduce the number of breeding sites, and reducing the case fatality rate by improving case management.