The most widely quoted date for the beginning of the recorded history of avian influenza (AI) is 1878, when researchers first differentiated a disease of poultry (initially known as fowl plague but later renamed highly pathogenic avian influenza) from other diseases with high mortality rates. Current evidence indicates that highly pathogenic AI (HPAI) viruses arise through mutation after low pathogenicity AI viruses of H5 or H7 subtype are introduced into poultry. Between 1877 and 1958, a number of epizootics of HPAI occurred in most parts of the world. From 1959 to 1995, the emergence of HPAI viruses was recorded on 15 occasions, but losses were minimal. In contrast, between 1996 and 2008, HPAI viruses emerged at least 11 times and four of these outbreaks involved many millions of birds. Events during this recent period are overshadowed by the current epizootic of HPAI due to an H5N1 virus that has spread throughout Asia and into Europe and Africa, affecting over 60 countries and causing the loss of hundreds of millions of birds. All sectors of the poultry population have been affected, but free-range commercial ducks, village poultry, live bird markets and fighting cocks seem especially significant in the spread of the virus. The role of wild birds has been extensively debated but it is likely that both wild birds and domestic poultry are responsible for its spread. Even without these H5N1 outbreaks, the period 1995 to 2008 will be considered significant in the history of HPAI because of the vast numbers of birds that died or were culled in three of the other ten epizootics during this time.