Technical Abstract: The natural host and reservoir for avian influenza is in wild birds where the viral infection is typically asymptomatic. The virus primarily replicates in the enteric tract and transmission is thought to be primarily by fecal-oral transmission. Avian influenza can infect a broad host range, but for most infections of abnormal host species, including poultry and mammals, it is a dead-end host because of poor replication and transmission. On rare occasions the virus can adapt to a new host species, and this adaptation process allows improved replication and improved transmission of the virus that can establish a unique virus, i.e swine influenza. The viral genetic factors that affect replication and transmission appear to be complex and are poorly understood at this time. The adaptation to poultry species and mammals usually results in a shift in viral tropism to the respiratory tract. The route of transmission likely also changes. Aerosol spread over short distances is possible, but transmission by direct contact or fomite transmission appears to be more important. The initial transmission of avian influenza to poultry is most often associated with direct exposure to wild birds, and the density of commercial poultry likely facilitates transmission of these viruses as they become more poultry adapted. Even for well adapted influenza viruses, they appear to become endemic in hosts that congregate in large numbers, both in wild birds, poultry, and mammalian species.