The differentiation, hematologic features and clinical manifestations of patients with the various sickling disorders are reviewed. The deficiencies in our current knowledge about the spectrum of the clinical course of patients with these conditions is discussed. The interaction ofαthalassemia with sickle cell anemia and its possible effect upon the severity of the disease is summarized. The apparent milder disease in certain groups of patients with sickle cell anemia in whom there is an associated elevation of hemoglobin F is contrasted with the controversy surrounding the effects of hemoglobin F levels in the patients of African origin.