During 2020, highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b viruses arose from previously circulating influenza A(H5Nx) viruses and spread predominantly via migratory birds to many parts of Africa, Asia and Europe. The epizootic has led to unprecedented numbers of deaths in wild birds and caused outbreaks in domestic poultry. In late 2021, these viruses crossed to North America and subsequently South America in October 2022. Additionally, globally, there have been increased detections of A(H5N1) viruses in non-avian species including wild and domestic (including companion and farmed) terrestrial and marine mammals and, more recently in goats and dairy cattle in the United States of America. The majority, with some regional exceptions, of the HPAI A(H5N1) viruses characterized genetically since 2020 belong to the 2.3.4.4b clade. Since the beginning of 2021, 28 detections of A(H5N1) in humans have been reported to WHO, including a case who had exposure to dairy cattle presumed to be infected with A(H5N1) virus. Of these human cases, where the haemagglutinin (HA) H5 clade is known, 13 have been caused by clade 2.3.4.4b viruses. This joint FAO/WHO/WOAH risk assessment focuses on A(H5N1) viruses characterized since 2021 and assesses the public health risk as well as the risk of the virus spread among animals.