There is overwhelming and compelling evidence that control efforts for sexually transmitted infection (STI) have a major role to play in the prevention of HIV transmission. Community-based randomized controlled trials are set as the highest standard of evidence for showing the efficacy of STI interventions to prevent HIV transmission. The negative results of recent randomized controlled trials have cast doubt on the positive findings of the Mwanza study. Deeper analysis of the result of these trials has improved understanding of the role of STI interventions and augmented the wealth of evidence provided by numerous epidemiologic and biomedical studies. Apart from the biologic impact of effective treatment of curable STIs on HIV transmission, clinical services also support the reduction of HIV risk behaviors. STI interventions should limit the scale of the impending epidemics in Asia and Eastern Europe, depending on the priority that they are given by governments and major donor agencies.