Phylogenetic studies of influenza A viruses have revealed species-specific lineages of viral genes, and that aquatic birds are the source of all influenza viruses in other animal species including humans, pigs, horses, sea mammals and birds. Influenza pandemics, defined as global outbreaks of the disease due to new antigenic subtypes, have exacted a high death toll from human populations. The most devastating pandemic, the so-called Spanish influenza of 1918 to 1919, resulted from an H1N1 virus and caused the deaths of at least 20 million people worldwide. Other much less catastrophic pandemics occurred in 1957 (Asian influenza [H2N2 virus]), 1968 (Hong Kong influenza [H3- N2 virus]), and 1977 (Russian influenza [H1N1 virus]). It is noteworthy that both the Asian and Hong Kong outbreaks were caused by hybrid viruses, or reassortants, that harbored a combination of avian and human viral genes. Avian influenza viruses are therefore key contributors to the emergence of human influenza pandemics. Fowl plague caused by highly pathogenic avian influenza A viruses is a constant threat to the poultry industry, but until the Hong Kong influenza outbreak, there was no zoonotic evidence that avian viruses could be transmitted directly to humans. In May 1997, an H5N1 influenza virus was isolated from a 3-year-old boy in Hong Kong, who died of extensive influenza pneumonia. By the end of 1997, a total of 18 cases of human influenza as an emerging infection had been identified, all caused by the same H5N1 virus. With this outbreak, it became clear that the virulence potential of these viruses extended to humans. The H5N1 isolates were not reassortants like the 1957 and 1968 pandemic strains; instead, all of the viral genes had originated from an avian virus. It will be critical to identify the molecular determinants that allow efficient transmission and replication of avian influenza viruses in humans, so that probable pandemics can be anticipated well before the death toll begins to mount. And health officials should begin to consider the production of emergency vaccines against all 15 existing HA subtypes of influenza virus. Also, given the existence of a vast number of influenza viruses in the aquatic wild-bird reservoir, we must accept the fact that they always pose pandemic threats. Thus, it is recommended that poultry (chickens, turkeys, etc.), domesticated ducks, and pigs be kept in ecologically controlled, secure houses with limited access to wild birds.