Neurological complications, especially stroke, have long been recognized in sickle cell disease. Advances in care have increased the life expectancy of such patients, and recent information has better established the epidemiology of stroke. Prevention of stroke in children has been established in a clinical trial. Silent brain lesions revealed by MRI are common and are associated with impairments of cognitive function. Transfusion remains the primary mode of prevention and treatment for stroke, although interest is increasing in hydroxyurea; however, there are no data regarding its efficacy.