This report addresses issues of pathogenesis, pathophysiology, and epidemiology of an increasingly prevalent cardiomyopathy in acquired immunodeficiency syndrome (AIDS). As patient survival increases with more effective antiretroviral therapy, cardiomyopathy in AIDS will become more apparent. The interactions of cellular and organism factors in AIDS and their relationships to the development of cardiomyopathy are reviewed herein. Amongst the factors addressed in this review are: (1) comorbid conditions found with AIDS, (2) the role of inflammatory heart disease and cytokines in the development of AIDS cardiomyopathy, (3) the pathogenetic role of vascular cells and myocardial cells in the development of cardiomyopathy, (4) the role of myocardial retroviral infection in AIDS, and (5) the impact of toxicity from antiretroviral therapy on the development of cardiomyopathy. Because it is possible that more than 1 of these factors is present in a given patient inflicted with AIDS, a multifactorial pathogenesis in AIDS cardiomyopathy must be considered.