The Roundtable on Population Health Improvement, a convening activity of the National Academies of Sciences, Engineering, and Medicine, held a workshop on March 15-16, 2021, to explore issues related to increasing health care spending in the United States. The workshop, U.S. Health Care Expenditures: Costs, Lessons, and Opportunities, was organized to highlight the persisting challenge of health care expenditures that are not commensurate with the health outcomes they produce. This publication summarizes the presentation and discussion of the workshop.