Joseph R. Biden was elected President of the United States during a period of compound crises for global health and security: the worst pandemic in a century, as well as steep reverses in progress toward reducing poverty, hunger, and disease. The United States has been in full retreat from global health leadership, fraying relationships with allies, weakening global institutions, and engaging in nationalist populism that threatens global cooperation to address worldwide challenges. Yet these tragic circumstances are also fertile soil for deep structural reforms. President Biden can both bolster the immediate responses to COVID-19 and its vast ramifications, and spearhead lasting changes to create a healthier and safer world, from which the United States would richly benefit. His immediate task will be to bring U.S. economic and scientific strength to the COVID-19 response in partnership with the World Health Organization (WHO). The Biden administration should also assume financial and strategic leadership in bolstering world efforts to achieve the Sustainable Development Goals (SDGs), including its singular pledge to leave no one behind. Finally, President Biden should empower the WHO and lead on reforms to the global health architecture to advance the right to health.