Global health challenges threaten the United States’ health and economic security, a reality made painfully clear over the past 14 months. Many low- and middle-income countries lack adequate domestic resources to invest in public health and, at the same time, face mounting debt burdens that impede their ability to raise new funding for essential investments. The Covid-19 pandemic is a call to action to rethink how the United States prioritizes pandemic preparedness and investments in public health. U.S. leadership will be essential to mobilizing investment from the official sector and private investors. Introduction Even after the Covid-19 pandemic is contained, the United States will remain vulnerable to global health security threats unless and until it prioritizes domestic and international investments in public health. Many low- and middle-income countries (LMICs) lack adequate domestic resources to invest in public health and, at the same time, face mounting debt levels that challenge their ability to raise new funding. While the Covid-19 pandemic represents a human tragedy on a global scale, it also is a call to action to rethink the roles of official and private sectors in financing global public health. At this moment of acute health and economic crises, the United States needs to think boldly about new approaches that will compel higher investment in essential areas, more aggressively leverage existing institutions, and mobilize additional resources to sustain investment in public health and pandemic preparedness.