Human influenza A viruses evolve rapidly by antigenic shift and antigenic drift. Antigenic shift occurs by genetic reassortment between currently circulating human viruses and influenza viruses of other origin, by re-emergence of a previously circulating virus, and by invasion of animal influenza viruses. The segmental structure of the virus genome enables reassortment in multiply infected cells and also promotes multiple infection because it results in yielding noninfectious particles which randomly lack some genome segment and only become infectious by complementation with others. Antigenic drift is due to an accumulation of nonsynonymous substitutions in the genes encoding the HA and NA proteins. The limited nature of infection to the respiratory epithelium which is the border of the immune system enables the virus to reinfect and grow under the partial immune pressure which results in selecting and expanding antigenic mutants.