Drug use continues to be a major factor fueling the global epidemic of HIV infection. This article reviews the current literature on the ability of drug treatment programs to reduce HIV transmission among injection and noninjection drug users. Most data come from research on the treatment of opiate dependence and provide strong evidence on the effectiveness of medication-assisted treatment for reducing the frequency of drug use, risk behaviors, and HIV infections. This has been a consistent finding since the epidemic began among diverse populations and cultural settings. Use of medications other than methadone (such as buprenorphine/naloxone and naltrexone) has increased in recent years with promising data on their effectiveness as HIV prevention and as new treatment options for communities heavily affected by opiate use and HIV infection. However, few treatment interventions for stimulant abuse and dependence have shown efficacy in reducing HIV risk. The cumulative literature provides strong support of drug treatment programs for improving access and adherence to antiretroviral treatment. Drug users in substance abuse treatment are significantly more likely to achieve sustained viral suppression, making viral transmission less likely. Although there are challenges to implementing drug treatment programs for maximum impact, the scientific literature leaves no doubt about the effectiveness of drug treatment as an HIV prevention strategy.