Outbreaks of H5N1 highly pathogenic avian influenza (HPAI) occurred in various types of domestic poultry in Thailand during 2004–05. H5N1 viruses were also detected in humans and other mammalian species. Infections were mainly detected in backyard chickens and domestic ducks. The geographic distribution of the 2004 outbreaks was widespread throughout Thailand; most outbreaks occurred in the Central Region, the southern part of the Northern Region, and the Eastern Region. In 2005, the H5N1 outbreaks continued and showed a clustered pattern in four provinces in the southern part of the Northern Region and in one province in the Central Region. H5N1 HPAI outbreaks caused serious socioeconomic consequences to the poultry industry, the social community, farmers' livelihood, and human health. After key measures were implemented, the incidence of the outbreaks declined remarkably in 2005.