Beta-thalassemia is a group of hereditary hemolytic anemia caused by beta-globin gene mutation, resulted in reduced or lacked synthesis of beta-globin chains. Clinical manifestations ranged from severe anemia to normal. Severe patients will die of anemia, septicemia or generalized organ failure if timely treatment is not available. Previous conservative treatments included life-long red blood cell transfusion, iron chelation, and splenectomy, etc. Due to iron overload, immunocompromise and low efficacy of conservative treatments, novel therapeutic approaches including pharmaceutical induction of gamma-globin, allogeneic hematopoietic stem cell transplantation and gene therapy have been developed. This review discussed current and future alternative therapies for beta-thalassemia major.