The International AIDS Society has launched a new global research strategy for working toward a broadly applicable cure for HIV. While antiretrovirals can keep HIV replication in check as long as treatment continues, the virus establishes a long-lasting reservoir in immune cells that is unreachable by antiretrovirals and usually invisible to the immune system. Over the years, researchers have identified two people who were cured of HIV after receiving stem cell transplants for cancer treatment as well as a small proportion of people who manage to naturally control the virus without antiretrovirals. Such cases are exceptional, but they offer proof of concept that a functional cure is possible and provide clues that may help others achieve long-term viral remission. Technological advances have improved the ability to detect tiny amounts of hidden virus, and new interventions—including broadly neutralizing antibodies, therapeutic vaccines, engineered immune cells and gene therapy—have shown early promise in animal studies.