Twenty-five years after the first cases were diagnosed in Los Angeles in 1981, FRONTLINE traces how a handful of mysterious deaths became a global pandemic that has killed tens of millions. The film moves from San Francisco bathhouses and New York hospital wards to the townships of South Africa and the villages of Uganda, using archival news footage and interviews with doctors, researchers, activists, and government officials who lived through each stage of the crisis. It covers the early years of denial and stigma, the Reagan administration's slow response, the rise of ACT UP and its confrontations with the FDA, and the scientific race that produced antiretroviral drugs in the 1990s. It also follows the pandemic's second act in the developing world, where drug pricing and political resistance to prevention programs turned treatment into a matter of geography. Told across two parts, the series lets people who buried friends, ran clinics, or sat in Washington offices during the debate explain what they knew and when they knew it.