We describe the case of a 39-year-old human immunodeficiency virus (HIV)-infected man with angiographically documented rapid progression of coronary artery disease. Over a time course of only 2 months, he developed high-grade stenosis of the left anterior descending coronary artery. The risk of myocardial infarction is increased in patients with HIV infection receiving antiretroviral therapy. However, the absolute risk is small and the marked overall benefits of antiretroviral therapy are evident. Patients receiving HIV protease inhibitors should be screened for hyperlipidemia, hyperglycemia, and hypertension. They may be candidates for lipid-lowering therapies depending on their long-term prognosis and individual risk of cardiovascular disease. Care is need because of possible drug interactions between lipid-lowering drugs and antiretroviral therapy. Invasive treatment of acute myocardial infarction does not differ from that in patients not infected with HIV. The rate of progression of coronary artery disease and the restenosis rate, however, are often unexpectedly high in these patients.