Cerebral infarction is a major cause of morbidity and mortality in children with sickle cell disease. Prevention of primary stroke might be feasible with a way to identify children at greatest risk. Transcranial Doppler (TCD) has been shown to be a noninvasive, reliable, inexpensive method of identifying children at highest risk for cerebral infarction. The pros and cons of imaging and non-imaging TCD techniques are discussed. The protocol for the stroke prevention trial in sickle cell anemia (STOP), including data acquisition and interpretation, is reviewed. Providing TCD to sickle cell patients can be a valuable service that results in a significant decrease in first stroke rates.