Both alcohol abuse and human immunodeficiency virus (HIV) infection have deleterious effects on brain structure, metabolism and function. In individuals with both afflictions these effects are doubtless additive and may interact to produce synergistic adverse effects. Further, the normal processes of aging produce brain degeneration that leaves older people especially vulnerable to the untoward effects of alcohol abuse and HIV infection. Advances in in vivo brain imaging now make practical the clinical study of the interaction of alcoholism and HIV infection and the potential of increased vulnerability produced by advancing age. In addition to structural magnetic resonance imaging (MRI), which provides quantitative assessments of brain macrostructure, are diffusion tensor imaging (DTI), which assesses microstructural integrity, magnetic resonance spectroscopy (MRS), which provides assessment of brain chemical moieties related to neuronal viability, and functional magnetic resonance imaging (fMRI), which provides assessment of localized blood oxygenation state association with performance of specific cognitive or motor tasks. Here, we first review postmortem observations on patients with HIV infection and with alcoholism to identify the cell types and brain regions most affected by the end stage of the disease. We then review in vivo neuroimaging studies of brain changes associated with HIV infection, chronic alcohol use, their interaction, and the potentiating effects of age. While there are many studies of people with either HIV infection or chronic alcohol use alone currently little has been published on the interactive effects of these variables, despite the high prevalence of overlap. We conclude with a consideration of the methodological issues such studies must address.