Clinical experience with hydroxyurea for patients with sickle cell disease (SCD) 
has been accumulating for the past 25 years. The bulk of the current evidence 
suggests that hydroxyurea is well-tolerated, safe, and efficacious for most 
patients with SCD. Hydroxyurea has proven clinical efficacy for reducing acute 
vaso-occlusive events including pain episodes and acute chest syndrome. Salutary 
effects on hematological parameters include increases in fetal hemoglobin (HbF), 
hemoglobin, and MCV; also significant decreases occur in WBC, ANC, 
reticulocytes, LDH, and bilirubin. Treatment with hydroxyurea is usually 
considered for patients with recurrent vaso-occlusive events, but additional 
indications for treatment may include laboratory markers of disease severity and 
evidence of chronic organ dysfunction. Ten years ago, the US Food and Drug 
Administration approved hydroxyurea for adult patients with clinically severe 
SCD; however, its use in children remains off-label. Despite the large body of 
evidence regarding its efficacy and safety, hydroxyurea is currently prescribed 
only sparingly for patients with SCD and therefore has only limited 
effectiveness for this disorder; barriers to its use need to be identified and 
overcome.