Sickle cell anemia and the thalassemias are globally the most common class of inherited disorders. Current treatment options are limited (transfusion, iron chelation) and are not suited to large-scale use in developing countries where the population of affected individuals is expected to undergo a tremendous increase in the near future. As such, the development of more practical and more permanent therapies is urgently needed. Recently, transgenic and gene knock-out technologies have been used to create mouse models for sickle cell anemia and all of the clinically relevant thalassemias (hemoglobin Bart's hydrops fetalis, hemoglobin H disease,[beta]-thalassemia intermedia,[beta]-thalassemia major/Cooley's anemia). These newly developed murine models should play an important role in the development of improved approaches for treating these commonly occurring genetic diseases.