In 2011, when the Joint United Nations Programme on HIV/AIDS (UNAIDS), the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), and our many partners joined forces to launch the Global Plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive (Global Plan), the goal of an AIDS-free generation was still distant. Today, the outlook for millions of pregnant women living with HIV, their children, and families, particularly in sub-Saharan Africa, has been dramatically transformed. In just 5 years under the framework of the Global Plan, 21 high-burden priority countries in sub-Saharan Africa reduced annual HIV infections among children by 60 percent. Across these countries, 1.2 million new HIV infections among children were averted, and over 2 million more pregnant women started receiving lifesaving antiretroviral therapy. Over the course of the Global Plan, 7 of the countries reduced new HIV infections among children by more than 70 percent (Uganda, 86 percent; Burundi, 84 percent; South Africa, 84 percent; Swaziland, 80 percent; Namibia, 79 percent; Mozambique, 75 percent; and Malawi, 71 percent). These are far more than just facts and figures; each infection averted and life saved means another child or mother who is healthy, thriving, and able to pursue their dreams. This did not happen automatically or easily. The Global Plan demonstrated that if we are ambitious, if we stay focused on the goal, and if we work together, we can make the impossible possible. The Global Plan's success depended on the extraordinary efforts and leadership of numerous partners across multiple sectors. Everyone played a critical role—host country governments and inspirational leaders, civil society and community organizations, faith-based organizations, health care providers, the private sector, women living with HIV, families and other loved ones, donors and technical agencies—and all were instrumental in what we achieved together. We are deeply grateful for, and profoundly humbled by, the countless contributions that so many have made—and continue to make—to this work. This diverse coalition of compassionate individuals brought us far closer to the day when no child is born with HIV, when every child who is already living with HIV receives lifesaving treatment, when every girl and boy can remain HIV-free throughout adolescence and young adulthood, and when every woman living with HIV—pregnant or not—receives the treatment and care that she needs and deserves. Yet, there is vital unfinished business and no time to waste. In a number of countries (Angola, Côte d'Ivoire, and Nigeria), progress has been slow, with less than a 40 percent reduction in new pediatric HIV infections over this same period. Every year, 110,000 children are still acquiring HIV in the 21 Global Plan priority countries, and 150,000 worldwide. More than half of new pediatric HIV infections occur during the breastfeeding period. Testing and treatment coverage among children remains too low. Alarming numbers of adolescent girls and young women are still being infected. That is why, in June 2016, PEPFAR and UNAIDS once again joined forces and launched Start Free Stay Free AIDS Free to accelerate the momentum driving this ambitious agenda, and bring even greater urgency and focus to the work ahead. The articles that comprise this Supplement trace the tremendous evolution and impact of the Global Plan across various domains, highlighting examples of bold leadership, innovation, and activism. They also capture the growth of a learning agenda, continually building on new developments in science, and translating these into lifesaving services. Together, they represent a living legacy of what has been done—and what must still be done—to reach our ultimate goals: controlling and then, finally, ending the AIDS epidemic as a public health threat by 2030 within the framework of the Sustainable Development Goals.