Life expectancy in the US fell by 2.26 years from 2019 to 2022, the biggest drop since WW II. COVID-19 accounts for 74 percent of the drop, but chronic conditions—e.g., diabetes, heart disease, kidney disease—have heavy health and economic costs. Of $4.1 trillion in US annual health expenditures, 90 percent goes to chronic conditions, including mental health. The numbers of US adults with diabetes and obesity are at epidemic levels. These conditions, along with COVID-19, are significantly increasing the prevalence of kidney disease. Population aging and lifestyle changes add to the increase, straining the health-care system. Trends are emerging toward upstream interventions using strategies to detect chronic diseases earlier and slow progression. Speakers will review trial approaches to improve population health and meet growing demands, e.g., for person-centered care and value-based payment models. They will discuss potential drivers of transformative change to modernize care, and clarify opportunities for reshaping chronic disease management.