Transmission and infection of H5N1 from infected avian sources to humans is a concern due to the global spread of H5N1 that constitutes a pandemic threat.

Infected birds pass on H5N1 through their saliva, nasal secretions, and faeces. Other birds may pick up the virus through direct contact with these excretions or when they have contact with surfaces contaminated with this material. Because migratory birds are among the carriers of the H5N1 virus it may spread to all parts of the world. Past outbreaks of avian flu have often originated in crowded conditions in southeast and east Asia, where humans, pigs, and poultry live in close quarters. In these conditions a virus is more likely to mutate into a form that more easily infects humans. A few isolated cases of suspected human to human transmission exist, with the latest such case in June 2006 (among members of a family in Sumatra). No pandemic strain of H5N1 has yet been found.

H5N1 vaccines for chickens exist and are sometimes used, although there are many difficulties, and it's difficult to decide whether it helps more or hurts more. H5N1 pre-pandemic vaccines exist in quantities sufficient to inoculate a few million people and might be useful for priming to "boost the immune response to a different H5N1 vaccine tailor-made years later to thwart an emerging pandemic". H5N1 pandemic vaccines and technologies to rapidly create them are in the H5N1 clinical trials stage but can not be verified as useful until after there exists a pandemic strain.