Since the early years of the human immunodeficiency virus (HIV) epidemic, stigma has been understood to be a major barrier to successful HIV prevention, care, and treatment. This article highlights findings from more than 10 studies in Asia, Africa, and Latin America—conducted from 1997 through 2007 as part of the Horizons program—that have contributed to clarifying the relationship between stigma and HIV, determining how best to measure stigma among varied populations, and designing and evaluating the impact of stigma reduction-focused program strategies. Studies showed significant associations between HIV-related stigma and less use of voluntary counseling and testing, less willingness to disclose test results, and incorrect knowledge about transmission. Programmatic lessons learned included how to assist institutions with recognizing stigma, the importance of confronting both fears of contagion and negative social judgments, and how best to engage people living with HIV in programs. The portfolio of work reveals the potential and importance of directly addressing stigma reduction in HIV programs.