Since Spring 2024, new genotypes of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b have been identified in the United States (US). These HPAI H5N1 genotypes have caused unprecedented multi-state outbreaks in poultry and dairy farms, and human infections. Here, we discuss the current situation of this outbreak and emphasizes the need for pre-pandemic preparedness to control HPAI H5N1 in both poultry and dairy farms in the US.