This chapter reviews the epidemiology and genetic variability of the influenza virus types, contrasts their rates and patterns of evolution, and considers mechanisms which could account for the differences. It provides the differences of influenza A and C viruses. The quasispecies concept suggests that the high mutation rate of RNA viruses results in populations consisting of multiple genetic variants. Influenza viruses are similar in morphology, composition, and in their replication processes and are clearly evolutionarily related. The epidemiology of influenza A viruses has been well characterized due to the association of these viruses with pandemic outbreaks of disease in man. Serological studies have shown that antigenic variation can occur among isolates, influenza C viruses appear more antigenically stable than A viruses, and hemagglutinin subtypes of C viruses have not been observed. The pandemics usually result from the appearance of a new subtype strain containing a novel HA and/or neuraminidase that is immunologically different from that of previous circulating isolates.