Technical Abstract: Like many other RNA viruses, the success of influenza is associated with the virus' ability to undergo antigenic changes. For these reason, human influenza vaccines are evaluated every year to update the vaccine formulation to include vaccine seed that is more similar to currently prevailing strains. In contrast, broad subtype-specific immunity has been observed for avian influenza (AI) vaccines through experimental and field experience. Poultry are usually naïve to influenza virus due to their short production lives, and vaccination has rarely been used for the long-term control of AI. This has likely resulted in less immune selection pressure on the AI virus as compared to human influenza virus, and may partially explain the broader protection of AI vaccine in poultry. However, our recent findings indicate antigenic drift away from the vaccine strain, which has not been observed in AI virus, can occur in poultry. Thus, vaccination can lead to the evolution of antigenically divergent strains. However, it is also possible to control and eradicate the virus by judicious use of vaccination coupled with strong surveillance program. This paper discusses the effectiveness of currently available AI vaccines and suggests the ideal use of the vaccine even with antigenic drift of the virus.