U.S. leadership in global health advances core U.S. interests. It fulfills shared humanitarian values by saving and enhancing lives. It strengthens health security against common and emerging threats. And it promotes stability and prosperity in far-flung communities in the developing world who strive for better health and better lives for their families. For all these reasons, supporting global health should remain a U.S. government and budget priority—and as the second Obama administration and incoming Congress commence their work, this collection of essays offers pragmatic, informed guidelines for seizing the opportunities ahead. The volume analyzes seven important dimensions of a complex, widening U.S. global health agenda: HIV/AIDS; malaria; polio eradication; women’s health; health security; health diplomacy; and multilateral partners. Each essay catalogs and interprets the past four years’ developments in its respective focal area, charting the measurable health impacts for which the United States can claim at least partial credit, and highlighting persistent problems and challenges. The essays conclude with concrete recommendations on how the United States can achieve the best results in the next four years in promoting the improvement of health, especially among the world’s most vulnerable citizens.