Bhattacharya P, Sarmah D, Dave KR, et al. - The pathophysiology, epidemiology, evaluation, and treatment of sickle cell anemia (SCA)-related stroke in developed and developing countries are all examined in this comprehensive study. Transcranial Doppler ultrasound (TCD) has reduced the incidence of ischemic stroke from 11% to 1% because it identifies children at risk for stroke and allows for interventions to reduce this risk. Children with abnormally high TCD velocities (≥ 200 cm/s) are at an increased risk of stroke and may benefit from hydroxyurea or hydroxycarbamide (HU) after a period of a successful transition from chronic transfusions. If proven efficacious and safe, gene therapy may be offered to patients with SCA who have had a stroke or are at high risk of having a stroke. However, due to the high cost of gene therapy, it is unlikely to be implemented in low-income countries. In developing countries, HU is used for both primary and secondary stroke prevention. Expanding TCD implementation should be a top priority in those settings.