Mosquito and tick-borne flaviviruses are the causative agents of some of the world’s most important diseases, including dengue fever, yellow fever, Japanese encephalitis, tick-borne encephalitis and West Nile fever. Cumulatively, these viruses cause many millions of infections each year and impose a significant burden on public health resources, particularly in developing and newly developed countries. Vaccine development to eliminate flaviviral infections has been marked by uneven progress and a large number of setbacks. To date, no single approach has proved successful in leading to vaccine development against a wide range of flaviviruses, but the application of modern techniques to the problem is opening up new avenues of approach. This review summarizes some of the developments in vaccine research aimed at inducing protective immunity against flaviviral infections.