Aortic arch atheroma has more recently been identified as an independent risk factor for ischemic stroke. Initially, this was a result of careful autopsy observations, then followed by a series of in vivo studies in which aortic arch atheroma was identified by transesophageal echocardiography. The association of aortic arch atheroma with ischemic stroke is most likely causal, given that the stroke risk increases with increasing thickness of arch atheroma. There is quite a sharp increase in stroke risk for atheroma of 4 mm or greater compared with lesser thicknesses. The clinical diagnosis is suggested when transient ischemic attack or ischemic stroke has occurred in which no obvious cardiac or arterial source of embolism is found. The presence of aortic arch atheroma is usually detected by transesophageal echocardiography and sometimes by magnetic resonance imaging or computed tomography. There is uncertainty about clinical management, particularly for secondary prevention. Options include the use of antiplatelet agents, anticoagulants, thrombolysis, or surgery. The latter two options have only been described rarely in case reports. Of the less invasive approaches, combination antiplatelet therapy with aspirin and clopidogrel is favored, or the use of warfarin. The Aortic arch Related Cerebral Hazard (ARCH) trial is being conducted to determine which of these is more effective in minimizing a composite outcome cluster of ischemic stroke, intracranial hemorrhage, myocardial infarction, peripheral embolism, or vascular death. Other more general management strategies should include reasonably aggressive risk factor control with blood pressure and lipid-lowering therapies and, if indicated, careful diabetic control.