Allogeneic hematopoietic SCT remains the only treatment that can correct the hematological manifestations in patients with thalassemia major. Improving the clinical outcomes of high-risk, heavily transfused patients with liver fibrosis and inadequate iron chelation remains a challenge. Because of the relatively high probability of graft rejection and regimen-related toxicity in many patients receiving SCT for advanced thalassemia major, further development of new treatment regimens is warranted. This review addresses the reported clinical studies in patients with advanced thalassemia major and we have summarized our suggested conditioning approach to improve the outcome after SCT.