Although viruses in the genus Flavivirus share complex antigenic interrelationships, they can be divided into four phylogenetic/ecological groups: two mosquito-borne groups, a tick-borne group, and nonvectored viruses. These divisions largely reflect the selective constraints imposed on the viruses by the vertebrate hosts, the invertebrate vectors, and the associated ecologies. Phylogenetic trees based on the flavivirus genetic sequence show characteristic branching patterns that reflect these groupings. This review describes the evolution and possible origins of individual flaviviruses, correlating ecological and epidemiological characteristics with their phylogenies and geographic dispersal. It will also become apparent that many of the phylogenetic lineages that define species diverged relatively recently, and the subsequent dispersal and epidemiology of these viruses have therefore been significantly influenced by increasing human population densities and activities such as recreation, urbanization, land reclamation, transportation, and deforestation. This review also considers some of the likely implications of persistent/chronic infections in relation to virus dispersal and recombination between related flaviviruses on phylogenetic analysis and vaccine development strategies.