This report describes the health emergency caused by the first appearance and spread of HPAI subtype H5N1 in Central American, Caribbean and South American countries between October 2022 and September 2024, and presents the work carried out with the 15 countries that participated in FAO cooperation projects to support the prevention and control strategies implemented in the face of the entry of HPAI. It addresses the experience accumulated in critical aspects presented during the emergency, together with the challenges that arise for the prevention and mitigation of the risks of future incursions of highly pathogenic strains of HPAI in the region.