The dengue, West Nile, Japanese encephalitis and yellow fever viruses are important mosquito-borne viruses whose epidemiology is shifting in response to changing societal factors, such as increasing commerce, urbanization of rural areas, and population growth. All four viruses are expanding geographically, as exemplified by the emergence of West Nile virus in the Americas and Japanese encephalitis virus in Australasia. The large, recent global outbreaks of severe neurological disease caused by West Nile virus, the increasing frequency of dengue hemorrhagic fever outbreaks in the Americas, and the emergence of yellow fever virus vaccination-associated viscerotropic disease, are new clinical epidemiologic trends. These worrisome epidemiologic trends will probably continue in coming decades, as a reversal of their societal and biological drivers is not in sight. Nevertheless, the substantial reductions in Japanese encephalitis virus incidence resulting from vaccination programs and economic development in some Asian countries provide some encouragement within this overall guarded outlook.