There has been a remarkable increase in tick-borne flaviviral disease incidence throughout the past 2 decades. Transmission of tick-borne viruses, like other vector-borne agents, is impacted by a very broad set of factors, both natural (eg, climate and ecology) and man-made (eg, human mobility and agricultural patterns). As our encroachment into areas of virus endemicity intensifies, and as changes in global economic and environmental conditions continue to promote the expansion of tick populations, we will undoubtedly continue to observe attendant increases in rates of disease attributable to these vector-borne pathogens. This article focuses on a some of the major tick-borne flaviviral diseases, caused in particular by tick-borne encephalitis virus, louping ill virus, Powassan virus, Kyasanur Forest disease virus, and Omsk hemorrhagic fever virus, as well as their subtypes.