Scientific strides in HIV treatment and prevention have reduced transmissions and HIV-related deaths significantly in the United States in the past two decades. However, despite coordinated national efforts to implement HIV services, the epidemic persists, especially in the South. It also disproportionately impacts marginalized groups, such as Black/African-American and Latinx communities, women, people who use drugs, men who have sex with men, and other sexual and gender minorities. Following the release of the HIV National Strategic Plan and marking two years since the launch of the Ending the HIV Epidemic: A Plan for America (EHE)—a U.S. Department of Health and Human Services initiative to reduce new HIV transmissions by at least 90% by 2030—researchers, advocates, and other stakeholders reported on the HIV epidemic response in The Lancet HIV in the U.S. Series, published online today.