Almost 30 years have passed since the first successful hematopoietic stem cell transplantation in thalassemia and that first patient is now a healthy young adult with a completely normal life. Since that time, more than 3000 such transplants have been performed worldwide. This review provides a brief history of hematopoietic stem cell transplantation in thalassemia and reassesses current clinical results with the objective to provide outcome predictions based on modern transplant technologies. The role of hematopoietic stem cell transplantation in the oral chelation era and implications for possible closure in the approach to future gene therapy will also be discussed.