Cerebral vascular disease is a common and serious complication of sickle cell disease that mainly involves the large blood vessels of the skull base. Because recurrences are common and residual deficits severe, attention has turned to detection of preclinical cerebral involvement with the goal of preventing clinical damage. Magnetic resonance imaging (MRI), an extremely sensitive tool for detecting cerebral infarction/ischemia, has shown that 10% of asymptomatic patients exhibit white matter lesions that seem to be associated with impaired cognitive function and may be predictive of stroke; magnetic resonance angiography demonstrates occlusions of skull base arteries but is not reliable for the diagnosis of stenosis because of artifacts generated by rapid turbulent flow. Transcranial Doppler is sensitive and specific for the detection of arterial stenosis and occlusion, even in asymptomatic patients. Digitized cerebral angiography remains the gold standard investigation for pretreatment confirmation of lesions detected by Doppler and/or MRI.