Growth and pubertal disturbances are the commonest endocrinopathies in homozygous thalassemia, accounting for significant morbidity in 70-80% children and adolescents globally. This review focuses on the pathophysiology of the endocrinopathy from a historical perspective and altered natural history induced by better care due to transfusion and chelation therapy. We have also discussed clinical features, diagnosis, and management strategies of growth retardation, sexual infantilism, pubertal aberrations, and scope of growth hormone, sex steroids, and other endocrine therapies. The article also emphasizes current and future strategies for screening, monitoring of growth and pubertal disturbances, and early intervention for the restoration of fertility potential and bone mass in the affected individuals.