The HIV prevention landscape has changed substantially over the last several years with several major successful and negative efficacy trials. The field is addressing a number of central research questions:  First is the question of what populations bear the heaviest burden of new HIV infections, and the underlying causes for the heterogeneity in the intensity of the epidemic. Is the heterogeneity explained by the prevalence of behaviors or biomedical co-factors, prevalence of HIV testing, disclosure, and access to ART, or as yet undefined differences between populations? One reason to explore underlying reasons for heavily concentrated epidemics is that these insights may point to new, effective interventions. A second set of questions focuses on the appropriate balance between discovery and development of research approaches within the HIV prevention field. When is there sufficient evidence to launch efficacy trials? What is the role of multiple trials of similar approaches? How can we maximize information from both positive and negative trials? A third set of questions focuses on pre-exposure prophylaxis (PrEP), a promising but yet unproven prevention strategy using ARV in HIV-negative persons. Several large trials are currently underway or soon to be launched, with nearly 20,000 volunteers targeted for enrollment in the current generation of trials. These trials will address a suite of research questions, and raise several more, including the role of continuous vs intermittent PrEP, topical vs oral PrEP, selection of specific drugs, and the influence of PrEP on risk practices. This suite of trials also raises questions about how results from any single trial will affect other trials, and the weight of evidence required to change the standard control condition for prevention trials. A final set of questions focuses on how best to integrate HIV prevention into diagnosis, care, and treatment of HIV-infected persons globally. Recent progress in each of these areas will be discussed.