Influenza A viruses cause chronic, asymptomatic infection in the gastrointestinal tracts of wild birds, but are also able to infect and cause disease in a variety of mammals. Such avian viruses cause a range of illness in humans, ranging from conjunctivitis through the fulminant illness caused by the recently emerged H5N1 virus. On rare occasions, an influenza A virus is introduced into human populations and spreads rapidly to cause a global pandemic. This can occur either when an avian virus with a novel HA protein adapts to human-to-human transmission, or when an avian virus undergoes genomic reassortment during co-infection of an influenza virus-infected mammal such as a pig. As a pandemic virus circulates, it undergoes progressive antigenic drift in its HA and NA proteins, permitting to re-infect the same populations in regular outbreaks of “seasonal” influenza.