Sickle cell anaemia (SCA) is the most common cause of childhood stroke, occurring with the highest frequency before the age of 6 years. Despite the relative frequency of stroke in SCA, few predictors of risk exist. Anaemia, leucocytosis, hypertension, silent infarction, and history of acute chest syndrome are well-documented risk factors for ischaemic stroke in SCA. Recent data suggest that other environmental and genetic factors, many unrelated to SCA, influence the development of cerebrovascular disease. Non-invasive assessment of individual stroke risk using transcranial Doppler ultrasonography has provided a means of selecting and prophylactically treating SCA children at highest risk. With the ultimate goal of preventing stroke, the information gained from the studies reviewed here may lead to improved prediction of stroke so that clinical trials to assess risk-based therapy may be carried out on selected children with SCA.