With the advent and widespread use of antiretroviral therapy (ART), the epidemiology of cardiomyopathy and heart failure (HF) associated with HIV infection is changing. Near-normal life expectancy in contemporary HIV-infected populations has been associated with prolonged exposure to increased cardiometabolic burden and chronic immune activation and systemic inflammation. Therefore, the pre-ART phenotype of HIV-associated cardiomyopathy with overt left ventricular systolic dysfunction and poor prognosis has been replaced over time by cardiomyopathy with a more insidious course, more frequent ischemic background, and highly prevalent left ventricular diastolic dysfunction. Patients with HIV are more prone to development of coronary artery disease and development of HF after myocardial infarction. The role of ongoing immune activation and systemic inflammation, despite highly active ART (HAART), appears to be central in this process. The role of HAART toxicity is controversial, as HAART itself appears to be protective for the development of HF, but recent data suggest that protease inhibitors might adversely affect the course of HIV-associated HF. Because of these unique features, the optimal therapeutic approach for HIV-associated cardiomyopathy remains unknown. The current therapeutic approaches are an extrapolation from noninfected populations. Importantly, the significance of the highly prevalent diastolic abnormalities among HIV-infected patients is not known. Therefore, further research is needed to identify its prognostic implications. Considering the prevalence of structural and functional cardiac abnormalities in HIV-infected persons and the lack of evidence on how to best screen and treat these patients, systematic research on this topic is a public health priority.