Twenty years ago, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) was established to lead the global response to the HIV epidemic. Today, PEPFAR is a public health engine: a critical platform for strengthening health systems, preparing for and responding to pandemics, and enabling global health security. Here, we share how PEPFAR made it possible for FHI 360’s teams to effectively respond to COVID-19 in countries with established HIV infrastructure.