Tick-borne encephalitis (TBE) poses a growing health problem in many European countries and parts of Northern Asia. Thus, vaccination has been employed successfully for many years in endemic countries. Long-term experience gained from widespread use, however, prompted the development of improved vaccine formulations of the two licensed European TBE vaccines. Moreover, recent clinical trials also suggested the maintenance of high values of postvaccination neutralizing TBE antibodies for a longer period than expected; thus, also resulting in modifications with regards to immunization regimens. Recent advances in recombinant DNA technology have opened up future opportunities for developing novel live-attenuated vaccines against TBE virus and other flaviviruses. Animal experiments demonstrated safety and high immunogenicity profiles for these mutants; thus, making them promising vaccine candidates that will need to demonstrate a clear advantage if they are going to be alternatives to the traditional vaccines. Systematic TBE case monitoring by raising problem awareness, both inside and outside endemic regions, appears essential to provide evidence for a widely accepted TBE travel-vaccination recommendation in the future.