The National Institute of Allergy and Infectious Diseases has prepared for HIV vaccine efficacy trials with the hope of having a product which is deemed worthy of testing. This has entailed development of new field research infrastructure and training, in collaboration with many partners. Notably, experts in observational research and experts in field HIV prevention research have joined together in efforts to share their mutually reinforcing experiences. In crafting these potential trial sites, it has become evident that the same criteria that apply in vaccine site suitability should also apply to other prevention clinical trials. These criteria include novel approaches to barriers to sexual transmission, including topical microbicides/spermicides, treatment of sexually transmitted infections, reduction in intrapartum blood contamination, and various strategies to ensure clean needle use. Like vaccines, most of these interventions are theoretically plausible, but remain untested. With or without large scale vaccine trials, these other prevention technologies remain high priorities for HIV research.