Alcohol and other drug use have played a critical role in the risk, progression and treatment of HIV infection. In 2009, injection drug users (IDUs) accounted for 13% of new HIV infections in the United States and it remains a global problem. Risky alcohol use is more common in HIV-infected than non-infected, a behavior often reported in more than 25%. In this presentation, I will review the multidimensional effects of alcohol and drug use on a number of facets of HIV disease: epidemiology, sex risk behaviors, HIV disease progression, and mental health, specifically depression. In addition, I will review the effects on the liver of alcohol and drug use in the setting of HIV infection, both in the presence and absence of hepatitis. Finally, HIV treatment in the context of alcohol and drug use and addiction treatment in the context of HIV infection will be considered. Strategies and interventions to promote recovery, longevity, and prevention will be presented.