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In this article, we review the literature, which generally supports associations between female sex and cognitive dysfunction after cranial irradiation, cardiovascular outcomes, obesity, radiation-associated differences in pubertal timing, development of primary hypothyroidism, breast cancer as a second malignant neoplasm and suggests an increased prevalence for the development of osteonecrosis among females. Results of this review support future investigations to further define sex as a risk factor for other common treatment-specific exposures and outcomes. Additionally, research should focus on understanding the underlying biologic and physiological basis of these sex-specific risks. Historically, evidence from both basic science and clinical research has been used to develop risk-stratified therapy, allowing reduction of toxic therapies to low-risk patients without compromising overall survival. 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