The protracted coronavirus disease pandemic (COVID-19) has claimed nearly 1.5 million lives in Latin America and the Caribbean and has generated more than 44 million confirmed cases since its emergence in the region in February 2020. The region accounts for nearly 20% of confirmed cases of COVID-19 and about 30% of deaths worldwide, despite having only 8.4% of the world’s population. The conditions of vulnerability that characterize the Latin America and the Caribbean region have made it particularly susceptible to the effects of the pandemic. This unprecedented crisis has highlighted the central importance of the health and well-being of individuals and communities for economic performance and social development. This report showcases how the historical weaknesses of health systems, and the structural inequalities that characterize the region, have made it difficult to control the pandemic. In this second joint report, the Economic Commission for Latin America and the Caribbean (ECLAC) and the Pan American Health Organization (PAHO), provide an update on the evolution of the pandemic and its implications for health, society and the economy; define potential scenarios for control and evolution in the short term; and further elaborate on the recommended long-term lines of action to strengthen the State’s capacity to respond to the population’s health needs and their determinants, in the context of a transformative recovery.