A period of major change is unfolding in health and HIV services in South Africa, carrying opportunities and risks for delivering effective, integrated health services that improve health outcomes and save lives. South Africa is decentralizing HIV services to the primary health care level, paving the way for greater integration to address women’s health and to reduce maternal mortality. The United States can find feasible, flexible ways to support this process, even though its health program through the President’s Emergency Plan for AIDS Relief (PEPFAR) is scaling down. As PEPFAR transitions from an emergency to a more sustainable response, this is a crucial moment to demonstrate that it can address HIV-related goals by linking to more comprehensive services for women—notably linking HIV with family planning (FP), reproductive health (RH), and maternal child health (MCH). The stakes are high for PEPFAR and for the Global Health Initiative (GHI) to show results and, most importantly, for the women and children most at risk.