The hemoglobin disorders of beta-thalassemia and sickle cell disease together constitute the most prevalent of human monogenic diseases. Although palliative therapies and curative allogeneic stem cell transplantation therapy have been developed for these disorders, many patients still suffer significant morbidity and early mortality. Therefore, development of alternative treatment based on a gene therapy approach continues to be a worthwhile endeavor. Several laboratories have recently achieved major progress towards this goal. Using lentiviral vectors to obtain high-level expression of relatively complex globin gene cassettes, therapeutic correction of several murine models of both beta-thalassemia and sickle cell disease has been achieved. These breakthroughs, coupled with recent significant developments in the ability to select and expand genetically modified stem cells in vivo, have greatly advanced the possibility of gene therapy for the hemoglobin disorders in the near future. These advances, together with recent information regarding safety issues of retroviral gene transfer, are reviewed here.