Thalassemia patients with persistently high levels of fetal globin typically have less severe anemia, have milder clinical syndromes, and are often transfusion independent. Therefore, the search for molecules exhibiting the property of inducing gamma-globin gene expression and fetal hemoglobin (HbF) production is of great interest. Different pharmacological agents have been studied, namely erythropoietin, short chain fatty acids and cytotoxic agents, azacytidine, and hydroxycarbamide. Hemoglobin F inducers from natural plants, such as angelicin and resveratrol, are powerful inducers of erythroid differentiation and increase HbF in erythroid progenitors of thalassemia patients. Induction of HbF in beta-thalassemia patients is expected to be crucial for developing countries unable to sustain the high cost of clinical management of beta-thalassemia patients.