During 2020, highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b emerged and rapidly spread across many parts of Africa, Asia and Europe. In late 2021, the 2.3.4.4b A(H5N1) viruses were detected in Canada and have since spread across North and South America. In addition to infection of wild and domestic birds, these viruses have been detected in a number of mammals, many presumably infected through exposure to infected birds or contaminated environments. The most recent example of mammalian infection with clade 2.3.4.4b viruses is dairy cattle in the United States.