Thalassemia is one of the most common genetic disorders, worldwide.Beta-Thalassemia Major (BTM) is the most severe type, which reduces lifeexpectancy and quality of life. In this study, we searched the related keywords to subject from 1996-2019 in the Medline and Web of Science databases, therefore found 250 articles. Moreover, we categorized them into the studies on blood transfusions in beta-thalassemia and new treatment modalities in these patients. We concluded that blood transfusion is the most common therapeutic choice in BTM, but is associated with complications such as iron overload in vital organs. Heart, Liver, Pancreas, Bone Marrow, and Kidney are the main damaged organs.Irion overload related to cardiac dysfunction is the main cause of morbidity and mortality in BTM.Consequently, treatments such as cell therapy and CRISPR/Cas9 are more appropriate compared to the blood transfusion. Cell therapy with lentivirus vectors is one of the novel therapies. The main disadvantages are the differentiation of hematopoietic stem cells into induced Pluripotent Stem Cells (iPSCs), and the human leukocyte antigen mismatch. CRISPR/Cas9 could be used as a promising novel therapy of genetic diseases. CRISPR/Cas9 edits genomes, which is being rapidly grown in clinical use for the former in vivo modification of stem cell-mediated mutations that attempt to edit genes directly in endonuclease encoding. Therefore, in the present study, we described transfusion-related adverse effects in BTM and explained the advantages and disadvantages of new therapies.