Relevance. Despite the successes achieved over the 85-year history of the study of tick-borne encephalitis (TBE), there are still many controversial and unresolved issues. It is obvious that in the second decade of the XXI century, this natural focal neuroinfection, as before, poses a great threat to public health not only in Russia, but also in endemic countries of the world. Aim. To present modern aspects of etiology, epidemiology, diagnosis, specific prevention of TBE in Russia and endemic countries of the world. Conclusions. Currently, there are 4 genotypes of the TBE virus: Far Eastern, European, Siberian and Baikal, each of which has its own area, pathogenic potential for humans. Nosoareal of TBE covers most of the territory of Russia, 29 European countries. Cases of TBE disease or viral activity are registered in six Asian countries. For the correct verification of the diagnosis, criteria for the diagnosis of cases of the disease have been developed, which mainly concern unvaccinated persons. Since highly effective etiotropic drugs for the treatment of TBE have not yet been developed, the only strategy for reducing the incidence of TBE is mass vaccination of the population of endemic regions. Due to the increase in the rate of vaccination in Russia and European countries, in order to improve epidemiological surveillance of TBE, standards for specific laboratory diagnosis of the disease among vaccinated persons, clarification of the causes of the incidence of vaccinated, as well as deaths among them, need to be clarified. In conditions of combination of natural foci of TBE and other tick-borne infections, it is important to develop diagnostic algorithms, including differential diagnosis of this disease with other infections transmitted by Ixodic ticks.