Atherosclerosis is one of the most important and common causes of death and disability in the United States and throughout the world. More than 25 million persons in the United States have at least one clinical manifestation of atherosclerosis, and in many more, atherosclerosis remains an occult but important harbinger of significant cardiovascular events. Throughout the last half of the past century, coronary artery atherosclerosis has been a major focus for basic and clinical investigation. As a result, considerable strides have been made in the development of programs to prevent and treat the clinical manifestations of coronary artery disease. The development of lipid-lowering, antithrombotic, thrombolytic, and catheter-based therapies in particular has had considerable impact in reducing death and disability from coronary atherosclerosis. Yet atherosclerosis is a systemic disease with important sequelae in many other regional circulations, including those supplying the brain, kidneys, mesentery, and limbs. Persons with cerebral atherosclerosis are at increased risk for ischemic stroke. Those with renal artery atherosclerosis are at risk for severe and refractory hypertension as well as renal failure. Patients with atherosclerosis affecting the limb, ie, peripheral arterial disease (PAD), can develop disabling symptoms of claudication or critical limb ischemia and its associated threat to limb viability. Moreover, once disease is apparent in one vascular territory, there is increased risk for adverse events in other territories. For example, patients with PAD have a 4-fold greater risk of myocardial infarction and a 2- to 3-fold greater risk of stroke than patients without PAD.