During the last two decades conventional therapy has improved the prognosis of thalassemia. However, despite such improvement it still remains a progressive disease with treatment-related complications such as hepatitis, liver fibrosis, and cardiac disease. Bone marrow transplantation (BMT) can prevent or delay progression of the aforementioned complications. The importance of clinical research in the field of BMT was recognized with the award of the 1990 Nobel Prize in Physiology and Medicine to E. Donnall Thomas, one of the pioneers of BMT in humans. George Mathe' was a pioneer in the early development of clinical BMT. Mathe' et al. were the first to describe graft-versus-host-disease (GVHD) and its treatment, and the graft-versus- leukemia (GVL) effect in human. The first BMT for β-thalassemia major was performed successfully by Thomas et al. in Seattle, in 1981. In the same year another patient with β-thalassemia major underwent BMT in Pesaro, Italy, by Lucarelli et al. Since then, several hundred transplantations have been performed worldwide, the majority of these in Italy. From 1991 through 2007 BMT have been performed on 497 (Tehran=342, Shiraz=155) blood transfusion dependent patients with thalassemia major in Iran, with disease-free survival of 71-77% respectively. Due to high graft failure and GVHD rates, BMT from alternative donors should be restricted to patients who have poor life expectancies because they cannot receive adequate conventional treatment or because of alloimmunization to minor blood antigens. Beginning in the early 1980s, it was shown that umbilical cord blood contained high levels of hematopoietic progenitor cells.