Influenza A virus subtype H5N1, also known as A(H5N1) or H5N1, is a subtype of the Influenza A virus that is capable of causing illness in many species, including humans. An avian-adapted, highly pathogenic strain of H5N1 (called HPAI A(H5N1), for "highly pathogenic avian influenza virus of type A of subtype H5N1") is the causative agent of H5N1 flu, commonly known as "avian influenza" or simply "bird flu", and is endemic in many bird populations, especially in Southeast Asia.

An Asian lineage strain of HPAI A(H5N1) is spreading globally. It is epizootic (an epidemic in nonhumans) and panzootic (a disease affecting animals of many species, especially over a wide area) killing tens of millions of birds and spurring the culling of hundreds of millions of other birds in an attempt to control its spread. Most references in the media to "bird flu" and most references to H5N1 are about this specific strain.

HPAI A(H5N1) is an avian disease and there is no evidence suggesting either efficient human-to-human transmission of HPAI A(H5N1) or of airborne transmission of HPAI A(H5N1) to humans. Those infected with H5N1 have had, in almost all cases, extensive physical contact with infected birds. However, H5N1 has the potential to mutate or reassort into a strain capable of efficient human-to-human transmission. Due to the high lethality and virulence of human HPAI A(H5N1) infection to date, its endemic presence, its large and increasing biological host reservoir, and its significant ongoing mutations, the H5N1 virus is today the world's major current pandemic threat, and billions of dollars are being raised and spent researching H5N1 and preparing for a potential influenza pandemic.

In 2003, world-renowned virologist Robert Webster published an article titled "The world is teetering on the edge of a pandemic that could kill a large fraction of the human population" in American Scientist calling for adequate resources to fight what he saw as a major world threat to possibly billions of lives. On September 29, 2005, David Nabarro, the newly appointed Senior United Nations System Coordinator for Avian and Human Influenza, warned the world that an outbreak of avian influenza could kill anywhere between 5 million and 150 million people. Experts have identified key events (creating new clades, infecting new species, spreading to new areas) marking the progression of an avian flu virus towards becoming a pandemic flu virus, and many of those key events have occurred more rapidly than expected.