Influenza and Other Respiratory Viruses: Surveillance in the Americas 2021 is the fourth edition of this publication and depicts the latest intricacies of respiratory viruses’ surveillance and features differences in countries’ capacities and needs for improvement. In addition to regional trends in the first section, SARS-COV-2 disease (COVID-19) trends data and COVID-19 vaccination indicators are introduced. The subsequent report section, provides a variety of country-specific information from sociodemographic indicators to improvements in influenza at the human-animal interface. Understanding current surveillance capacities of respiratory viruses in the Region of the Americas provides a perspective to identify areas for action and guide cooperative efforts to bolster surveillance and impact evaluations.