Atherosclerotic disease accounts for ~25% of ischemic strokes. Atherosclerotic stroke is caused mainly by embolic events from the carotid artery bifurcation or the aortic arch, although intracranial thrombosis can occur, more often in African Americans, Asians, and diabetes patients. Primary prevention of stroke is critical for patients with risk factors for atherosclerosis, including hypertension, diabetes, smoking and hypercholesterolemia. Stroke can be prevented in patients with established atherosclerotic disease by identification and management of patients with carotid artery stenosis by non-invasive testing. Particular attention must be paid to patients with transient symptoms of brain ischemia.