Recognizing the need for increased cooperation, 30+ international organizations joined forces, forming the Global HIV Vaccine Enterprise (Enterprise), a voluntary alliance of public-and private-partners committed to working together, while maintaining independent decision-making authority. The Enterprise Secretariat (Secretariat) is a small organization that dedicates resources to facilitate coordination, collaboration, knowledge sharing, and resource optimization among the Enterprise. The overall goal of the Enterprise activity is identical with that of the NIAID: to stop the HIV epidemic through research to identify a safe and effective HIV vaccine capable of preventing HIV infection. All efforts of the activity seek to accelerate the development of preventive HIV vaccine candidates through mutual coordination, collaboration, knowledge sharing, and recruitment of new resources and funders to the field. Major outcomes of Enterprise efforts include (i) reducing or eliminating duplication of effort in vaccine clinical testing, (ii) optimizing the coordination of timelines for complex multi-partner clinical testing plans, to minimize or eliminate time lost, and (iii) promoting effective communications about progress and problems within the vaccine research field and with other stakeholders. To advance these goals the Enterprise works in close coordination with NIAID personnel, with HIV vaccine researchers, with vaccine developers and manufacturers, and with other major sponsors of HIV vaccine research. The Enterprise holds a unique central position, providing both support and leadership for strategic discussions, deliberations, and activities.