Uganda is one of the few countries in the world that has experienced a significant reduction in Human Immunodeficiency Virus (HIV) prevalence over the past decade. In contrast to many of its neighbors, Uganda has had an explicit national policy that includes: Abstinence, Be faithful, and Condoms. This strategy, known as “A,B,C,” has garnered wide attention in the United States as the efficacy of abstinence-based sex education is debated. This commentary is based on published and unpublished data together with personal observations derived from a Department of Health and Human Services (DHHS)-led delegation to Uganda in December 2002. The empirical bases for both an abstinence-only and a combined (A,B,C) strategy is reviewed; and the political consequences of the debate for both Africa and the United States are explored.