Abstract A workshop entitled Beyond 2010: Gaps, Challenges, and Priorities for the Future of Preclinical HIV Pre-Exposure Prophylaxis (PrEP) was sponsored by the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), on October 20-21, 2009, in Bethesda, Maryland. The objective of the workshop was to identify the main gaps in current knowledge, challenges, and priorities for the establishment of a PrEP preclinical pipeline and to also provide guidance for future directions of the field and DAIDS activities in this area. This 2-day workshop, through various presentations and breakout group discussions, specifically addressed four main topics that will be critical in identifying and advancing the next generation of PrEP candidates for clinical testing. The topics were (1) drug discovery, (2) pharmacokinetics (PK) and pharmacodynamics (PD), (3) animal models, and (4) delivery systems for prolonged activity. We report here a summary of the presentations and highlights of salient discussion topics from this workshop.