Technical Abstract: There have been 29 epizootics of H5 or H7 high pathogenicity avian influenza (HPAI) since 1959. The largest of these epizootics, affecting more birds and countries than the other 28 epizootics combined, has been the H5N1 HPAI which began in Guangdong China in 1996, and has killed or resulted in culling of over 250 million poultry and/or wild birds in 63 countries during the past 16 years. Most countries have used stamping-out programs in poultry to eradicate the H5N1 HPAI. However, 15 affected countries have utilized vaccination as a part of the control strategy; i.e. the countries have used >113 billion AI vaccine doses from 2002-2010. Mongolia, Kazakhstan, France, the Netherlands, Cote d’Ivoire, Sudan, North Korea, Israel, Russia and Pakistan have used <1% of the AI vaccine, and the AI vaccine was targeted to either preventive or emergency vaccination programs. Five countries have utilized nationwide vaccination programs which accounts for 99% of vaccine used: 1) China (90.9%); 2) Egypt (4.6%); 3) Indonesia (2.3%); 4) Vietnam (1.4%); and 5) Hong Kong SAR (<0.01%). Inactivated AI vaccines have accounted for 95.5% and live recombinant virus vaccines for 4.5% of vaccine used. Six countries have entrenched H5N1 HPAI. China, Indonesia, Egypt and Indonesia implemented vaccination after H5N1 HPAI became endemic in domestic poultry. Bangladesh and eastern India have entrenched H5N1 HPAI and have not used vaccination in their control programs. Clinical disease and mortality were prevented in chickens, and rural livelihoods and food security were maintained by using vaccines during HPAI outbreaks. However, field outbreaks have occurred in vaccinated flocks as the result of vaccine failure or improperly administration to the target species. Antigenic drift in field viruses has resulted in protection failure by classic H5 vaccines strains in Mexico, China, Egypt, Indonesia, Hong Kong and Vietnam.