Skeletal changes in beta-thalassemia major (βTM) create a wide spectrum of bone radiographic features. The main pathology is extensive marrow proliferation due to ineffective erythropoiesis but the relative skeletal findings are encountered with a progressively reduced frequency and severity nowadays due to the regular hypertransfusion programs. The resulting hemosiderosis and particularly iron chelation therapy have been associated with dysplastic features which are found more often. Skeletal radiological appearances in βTM relate to a complex multifactorial pathogenesis (i.e. marrow expansion, direct iron and chelation toxicity, endocrine complications) and depend on the severity and duration of the disease, the type and effectiveness of treatment and the toxic effects of chelation therapy. Awareness of these findings is very important since early recognition can be an indicator for therapy adaptation.