PURPOSE OF REVIEW: This review summarizes the development and implementation of a large clinical trial, HIV Prevention Trials Network (HPTN) 052, whose initial results were recently presented and published. RECENT FINDINGS: A randomized, clinical trial demonstrated that antiretroviral therapy reduces the sexual transmission of HIV in HIV-serodiscordant couples by more than 96%. The logistical challenges in preparing for and conducting such a trial were considerable. SUMMARY: HPTN 052 required many years of preparation, considerable collaboration between National Institute of Health and six pharmaceutical companies, and careful ongoing consideration of a large number of ethical issues. HPTN 052 revealed the magnitude of benefit when using antiretroviral therapy to prevent the transmission