The Global Plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive (Global Plan) has ensured that more infants in high-HIV burden countries survive childhood HIV-free. Although equal numbers of boy and girl children have survived to age 10, a gender divergence starts to emerge as they enter adolescence. Up to 3 times as many young women aged 15–24 years in eastern and southern Africa are living with HIV compared with their male peers. Further, more adolescent girls and young women are sick and/or dying from AIDS-related or HIV-related complications during pregnancy and in the postpartum period, underscoring the importance of strengthening HIV treatment and prevention services for this group. Failure to prevent HIV in adolescent girls and young women and keep them alive will reverse the infant HIV prevention and survival gains made under the Global Plan. The promising global declines in HIV infection in young women need to be strengthened to realize the goals of an AIDS-free generation. The DREAMS initiative of the United States President's Emergency Plan for AIDS Relief (PEPFAR), which specifically addresses adolescent girls and young women at highest risk of HIV acquisition, brings new hope for meeting the prevention and care needs of this important and vulnerable population through political commitment, leadership, financial and human resource investments, advocacy efforts, and a focus on the highest priority settings. Importantly, to achieve the goal of keeping mothers alive, we have to place more emphasis on access to sexual and reproductive health services that (1) include HIV prevention and treatment services for adolescent girls and young women; (2) increase male/paternal responsibility in mother and infant health; and (3) ensure a supportive social environment that enables young women to grow up into young adults who are free to graduate from high school and plan their pregnancies, ultimately entering adulthood safe, healthy, and free from HIV.