Tick-borne encephalitis virus is the virus associated with tick-borne encephalitis. TBEV is endemic in an area ranging from northern China and Japan, through far-eastern Russia to Europe, and is maintained in cycles involving Ixodid ticks (Ixodes ricinus and Ixodes persulcatus) and wild vertebrate hosts. The virus causes a potentially fatal neurological infection, with thousands of cases reported annually throughout Europe. It was initially isolated in 1937. Three virus sub-types are described: European or Western tick-borne encephalitis virus, Siberian tick-borne encephalitis virus, and Far eastern Tick-borne encephalitis virus (formerly known as Russian Spring Summer encephalitis virus, RSSEV). TBE has a significant mortality rate depending upon the strain of virus or may cause long-term neurological/neuropsychiatric sequelae in people affected. In this review, we comprehensively reviewed TBEV, its epidemiology and pathogenesis, the clinical manifestations of TBE, along with vaccination and prevention.