Influenza is a zoonotic respiratory virus that affects birds, mammals, and humans. Influenza viruses are unique in their genetic instability, which frequently results in antigenic drift or shift. Antigenic shifts are responsible for influenza epidemics. Influenza A pandemics have been responsible for millions of deaths during the past several hundred years. In terms of virulence and lethality, the 1918 to 1919 influenza pandemic was the worst in history. It was unique in its predilection and lethality among young healthy adults. There has never been a satisfactory explanation for the unusual virulence of the 1918 to 1919 pandemic.