This article presents major epidemiologic features of tick-borne encephalitis (TBE) in the Czech Republic, using data of laboratory-confirmed cases since 1970. A total of 17,053 cases of TBE were reported in the Czech Republic (population 10 million) in 1970–2008. The data show several important features. First, the pattern of TBE incidence changed over time. Until the end of the 1970s, TBE was characterized by periods of alternately higher and lower incidence (between 180 and 595 cases per year); the 1980s were a period of low incidence with minimum variability; since the beginning of the 1990s, there has been a steep rise in incidence, with marked year-to-year variation (e.g., 745 cases were registered in 1995, and a maximum of 1029 cases were registered in 2006). Second, the age distribution of TBE incidence has changed. Until the end of 1990s, incidence peaked among those 15–19 years of age, with a gradual decline with age. In the 2000s, however, TBE incidence has been rising in those aged 60–64 years, with a sharp decline in those older than 65 years. Third, the seasonal pattern of TBE has changed markedly over time. In the earlier period, incidence had a clear peak in July/August; since the 1990s, more cases have occurred in earlier and later months of the year. The proportion of cases occurring in April, May, October, and November increased from 9% in the 1970s to 23% in 2000–2008. Fourth, the geographical distribution of TBE also changed over time, with TBE increasingly occurring in the mountainous districts at higher altitudes. These changes in incidence patterns appear to be linked with changes in climatic and meteorological conditions. The link between climate change and TBE incidence is plausible, since TBE is a recreation-related infection associated with outdoor activities, and since climatic changes affect the life cycle of the vector.