COVID-19 illuminated gaps in emergency preparedness and healthcare delivery in the face of a global pandemic. This report from the Lancet Commission identifies strategies for strengthening the multilateral system to address global emergencies such as the COVID-19 pandemic. The report describes a conceptual framework for understanding pandemics; reviews global, regional, and national responses to the COVID-19 pandemic; and provides recommendations for ending the COVID-19 pandemic and preparing for future pandemics.