In this issue of Blood, Bernaudin et al report that chronic red blood cell transfusions can be safely replaced with hydroxyurea therapy or bone marrow transplantation for a cohort of children with sickle cell anemia (SCA) and abnormal transcranial Doppler (TCD) velocities. These data nicely complement the recently published results from the phase 3 multicenter TCD With Transfusions Changing to Hydroxyurea (TWiTCH) study and suggest that it may be safe to carefully transition a subset of patients from chronic transfusions to hydroxyurea therapy.