The burden of diabetes is enormous, positioning it as one of the main challenges facing public health today. Currently, it is estimated that 62 million people are living with diabetes in the Region of the Americas and projections show its prevalence will continue rising over the following years. The Region shows the highest number of years of healthy life lost (through either disability or premature death) due to diabetes worldwide. The high costs associated with its treatment produce a heavy economic burden. Its complications can seriously affect the quality of life of people living with diabetes, their families, and society and overload health systems. This report shows the latest internationally comparable data on diabetes and its main risk factors by year, country, and sex. It also includes a summary of the countries health systems’ response to diabetes, including national plans, targets, surveillance, guidelines, and access to essential drugs and technologies, and synthesizes information about diabetes-related complications and the close relationship between diabetes and other pathologies, such as cardiovascular diseases, tuberculosis, and COVID-19. The data presented here reveal that, despite advances in national responses, diabetes continues to expand, and our response remains insufficient. This report aims to draw attention to the urgent need to strengthen efforts to prevent, diagnose, and control diabetes in the Region of the Americas.