The 2021-2022 epidemic of highly pathogenic avian influenza was the most catastrophic in history, resulting in thousands of outbreaks and 69 million bird deaths in Europe. The virus mutated from subtype A (H5N8) to subtype A (H5N1) and has shown unprecedented mortality rates for wild birds and the ability to infect mammals. Recent outbreaks in the United States, Romania, and Mexico, as well as mass deaths of marine mammals in Argentina, Brazil, and Uruguay, further highlight the challenges in controlling and preventing the virus.