To review the effectiveness of projects and programs in developing countries that aim to reduce sexual transmission of HIV infection or transmission related to injection drug use. We identified 34 published studies undertaken in 18 developing countries that met rigorous inclusion criteria. These criteria included the length of follow-up, use of statistical analysis, the inclusion of a comparison group, and type of outcomes measured. We found that behavioral change interventions are effective when targeted to populations at high risk, particularly female sex workers and their clients. Few studies have evaluated harm reduction interventions in injecting drug users (IDUs). Evidence on the effectiveness of voluntary counseling and testing programs was promising, and VCT was most effective when directed at discordant couples. Treatment of sexually transmitted diseases (STD) appears highly effective in reducing HIV/STD transmission, particularly in the earlier stages of the epidemic. This review demonstrates that HIV prevention interventions can be effective in changing risk behaviors and preventing transmission in low and middle-income countries. When the appropriate mix of interventions is applied, they can lead to significant reductions in the prevalence of HIV at the national level. Additional research is needed to identify effective interventions, particularly in men who have sex with men, youth, IDUs and HIV-infected persons. Structural and environmental interventions show great promise, although more evaluation is needed.