Highly pathogenic avian influenza (HPAI) H5N1 expanded considerably during 2005 and early 2006 in both avian host species and geographic distribution. Domestic waterfowl and migratory birds are reservoirs, but lethality of this subtype appeared to initially limit migrant effectiveness as introductory hosts. This situation may have changed, as HPAI H5N1 has recently expanded across Eurasia and into Europe and Africa. Birds could introduce HPAI H5N1 to the Western Hemisphere through migration, vagrancy, and importation by people. Vagrants and migratory birds are not likely interhemispheric introductory hosts; import of infected domestic or pet birds is more probable. If reassortment or mutation were to produce a virus adapted for rapid transmission among humans, birds would be unlikely introductory hosts because of differences in viral transmission mechanisms among major host groups (i.e., gastrointestinal for birds, respiratory for humans). Another possible result of reassortment would be a less lethal form of avian influenza, more readily spread by birds.