This paper lays out the rationale and specific actions for fast-tracking combination HIV prevention to meet the UNAIDS target of reducing new HIV infections to fewer than 500,000 by 2020. Each section synthesizes and presents key epidemiological, clinical trial, and programmatic data; and uses examples and graphics to illustrate key points. The paper focuses on HIV prevention in adolescents and adults, and is broken down into six sections: commitment, focus, synergies, innovation, scale, and accountability. National commitments to HIV prevention need to be renewed through a focus on specific targets and resources, including program packages for policymakers to consider. Efforts should focus on key locations, priority populations, and high-impact programs and interventions. Synergies can be found in HIV prevention packages tailored to specific user groups and settings; the document provides examples for high-prevalence settings in southern Africa for men who have sex with men, young women and their male partners, people who inject drugs, and sex workers. It describes innovations in prevention tools, delivery approaches, and integration, including medical male circumcision, pre-exposure prophylaxis, digital social media, and cash transfers. Using examples, the paper underscores the importance of delivering products and programs at scale and with the intensity needed for impact. It concludes with an accountability framework that can be used to ensure that each program does its part and has the appropriate resources to do so.