A number of pharmacological agents are currently available for the induction of fetal hemoglobin (HbF) in patients with sickle cell disease and beta-thalassemia. Here we review the development of this new class of therapeutics and summarize the clinical trials that investigate their efficacy in patients with hemoglobin disorders. Hydroxyurea is the first of these drugs to be approved by the Food and Drug Administration for the treatment of sickle cell disease. Currently, the major focus is the development of safer agents and combinations of drugs that can increase HbF to levels high enough to prevent all complications of the disease. Progress in adapting the same strategy to the treatment of thalassemic disorders has been much slower. Although all the agents that are effective in sickle cell disease have similar HbF-inducing activity in beta-thalassemia, their use has rarely resulted in significant amelioration of the anemia. More research and more effective agents will be needed to make a significant impact on thalassemia. Nonetheless, success in this relatively young field has been very gratifying; before the end of this decade, clinically meaningful induction of HbF may become an achievable goal in most patients with hemoglobin disorders. Copyright 2001 by W.B. Saunders Company.