Individual leadership and leaders have played pivotal roles in the history of efforts to end the AIDS epidemic. The goal of this article is to reflect on and understand how leadership and leaders have impacted and enabled the success of the Global Plan Towards the Elimination of New HIV Infections among Children by 2015 and Keeping their Mothers Alive (Global Plan). To accomplish this goal, multiple interviews were conducted with individuals in positions of leadership who had been identified as people whose actions drove progress. Interviewees were selected from all levels of traditional hierarchies and sectors to provide a more complete account and representation of leadership, with a particular emphasis on the community, district, and country levels. The leaders interviewed provide insight into their work, motivations, and approaches to effective leadership. Through their experiences, they shed light on the strategies they used to drive changes in policy, programs, practice, and communities that allowed for progress toward the goals of the Global Plan. Leaders also identify future challenges and areas of improvement in the effort to end the AIDS epidemic that they feel require leadership and urgent action. In conclusion, this article identifies common characteristics of effective leadership and reflects on the experiences of individuals who are leaders in the effort to end the AIDS epidemic, and how their lessons learned can be applied to help realize future global public health goals.