The survival of patients with HIV infection who have access to highly active antiretroviral therapy has dramatically increased. In HIV-infected persons, cardiovascular disease can be associated with HIV infection, opportunistic infections or neoplasias, use of antiretroviral drugs or treatment of opportunistic complications, mode of HIV acquisition (such as intravenous drug use), or with the classic non–HIV-related cardiovascular risk factors (such as smoking or age). Diseases of the heart associated with HIV infection or its opportunistic complications include pericarditis and myocarditis. Pericarditis may lead to pericardial effusion rarely causing tamponade. Cardiomyopathy is often clinically silent with asymptomatic left ventricular systolic dysfunction. Endocarditis is mainly the consequence of intravenous drug abuse, possibly leading to life-threatening valvular insufficiency with the need for cardiac surgery. A further serious condition associated with HIV infection is pulmonary hypertension potentially leading to right heart failure. The cardiovascular complications of HIV infection such as cardiomyopathy and pericarditis have been reduced by highly active antiretroviral therapy, but premature coronary atherosclerosis is now a growing problem because antiretroviral drugs can lead to serious metabolic disturbances resembling those in the metabolic syndrome. Lipodystrophy, a clinical syndrome of peripheral fat wasting, central adiposity, dyslipidemia, and insulin resistance, is most prevalent among patients treated with protease inhibitors. These patients should thus be screened for hyperlipidemia, hyperglycemia, and hypertension, and they may be candidates for lipid-lowering therapies. When initiating lipid-lowering therapy, interactions between statins and HIV protease inhibitors affecting cytochrome P450 function must be considered. Restenosis rate after percutaneous coronary intervention may be unexpectedly high.