In the past 8 years, it has become apparent that some cytotoxic drugs that interfere with DNA replication can reprogram erythroid progenitors to switch from adult hemoglobin to fetal hemoglobin (HbF) production. Hydroxyurea has now been shown to substantially increase HbF in patients with sickle cell anemia. Since HbF interferes with sickle hemoglobin polymerization, hydroxyurea may become an important therapeutic agent for patients with sickle cell anemia.