Stroke is the third leading cause of death in the United States, constituting approximately 700,000 cases each year, of which about 500,000 are first attacks and 200,000 are recurrent attacks. Ischemic stroke accounts for the majority of all strokes (88%), followed by intracerebral hemorrhage (9%) and subarachnoid hemorrhage (3%). Patients with substantial carotid narrowing are at increased risk for major stroke; however, recent studies suggest that factors other than the degree of carotid stenosis are involved in ischemic stroke pathogenesis. Atherosclerotic plaque of the stenotic carotid artery is the underlying cause of the majority of ischemic strokes and specific plaque characteristics have been associated with ischemic brain injury. Several studies have demonstrated that the mechanisms of plaque instability in the carotid circulation are similar to those in the coronary circulation. The purpose of this review is to characterize atherosclerotic carotid disease in light of our knowledge of coronary atherosclerosis and relate carotid plaque morphology to cerebral ischemic syndromes. Histological examination of the carotid plaque specimen should provide insights into the underlying plaque morphology that is responsible for the disease and should help determine the potential treatments that are likely to be beneficial in the prevention of a subsequent event.