Thalassemia was clinically described almost 100 years ago and treatment of this genetic disease has seen a great progress during this period. DNA-based diagnosis proved the molecular basis of the disease and clarified the variable clinical picture. It also laid path for modern methods of carrier identification and prevention through DNA-based prenatal diagnosis. All aspects of supportive care, like safer blood supply, regular transfusions, monitoring of iron overload, parenteral as well as oral chelation, and other therapies, helped to prolong life and improve the quality of life of the patients. Many advances are also seen in allogenic bone marrow transplantation, which is the only curative therapy. Recent research has mainly focused on studying thalassemia at the basic science level, which resulted in the identification of unknown mechanisms leading to anemia and enabling the development of novel therapies which helps to improve the treatment of, and possibly cure the disease. Various pathways involving activin receptors, JAK2 inhibitors, heat shock proteins and macrophage targeted therapy, etc are under study or are currently undergoing clinical trials for treating thalassemia. Novel genetic therapies are being investigated.