Sickle cell disease (SCD) and ß-thalassemia represent the most common 
hemoglobinopathies caused, respectively, by the alteration of structural 
features or deficient production of the ß-chain of the Hb molecule. Other 
hemoglobinopathies are characterized by different mutations in the α- or 
ß-globin genes and are associated with anemia and might require periodic or 
chronic blood transfusions. Therefore, ß-thalassemia, SCD and other 
hemoglobinopathies are excellent candidates for genetic approaches since they 
are monogenic disorders and, potentially, could be cured by introducing or 
correcting a single gene into the hematopoietic compartment or a single stem 
cell. Initial attempts at gene transfer of these hemoglobinopathies have proved 
unsuccessful due to limitations of available gene transfer vectors. With the 
advent of lentiviral vectors many of the initial limitations have been overcame. 
New approaches have also focused on targeting the specific mutation in the 
ß-globin genes, correcting the DNA sequence or manipulating the fate of RNA 
translation and splicing to restore ß-globin chain synthesis. These techniques 
have the potential to correct the defect into hematopoietic stem cells or be 
utilized to modify stem cells generated from patients affected by these 
disorders. This review discusses gene therapy strategies for the 
hemoglobinopathies, including the use of lentiviral vectors, generation of 
induced pluripotent stem cells (iPS) cells, gene targeting, splice-switching and 
stop codon readthrough.