Lately, the magnitude of cumulative diseases burden caused by flaviviruses, such as dengue virus, Japanese encephalitis virus, tick-borne encephalitis virus, West Nile virus and yellow fever virus, has reached an unprecedented level with the sizes of human and animal populations at risk increasing sharply. These diseases present highly complex medical, economic and ecologic problems, some effecting primarily human and others affecting human, livestock and wildlife. The large body of recent publications on the development of vaccines taking advantage of new generations of bio-engineering techniques clearly reflects the profound interests and deep sense of urgency in the scientific and medical communities in combating those diseases. This review reveals a collection of remarkable progresses thus far made in flaviviral vaccine research not only employing a diverse range of new strategies but also re-tooling old techniques to improve the existing vaccines. The efficacy and safety of some of the new vaccine candidates have been evaluated and proven in human clinical trials. Besides the technical advancement in vaccine development, in this review, the importance of somewhat neglected and yet critical subjects, such as adequacy of animal model, vaccine safety, vaccine formulation and delivery, complication in serodiagostics and economic factor, was examined in-depth.