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Since its introduction more than 50 years ago, hematopoietic stem-cell transplantation (HSCT) has transformed from an inescapably fatal procedure to one where cure from malignant and other nonmalignant hematologic diseases is becoming increasingly common. Nevertheless, longevity is not entirely restored. New causes of mortality have emerged; of particular importance is that of increased cardiovascular disease (CVD), related to metabolic syndrome and its components. Controversy exists over whether the metabolic abnormalities induced are a direct effect of HSCT itself or a consequence of other therapies involved. Analysis of the mechanisms that promote the changes in metabolic components will give insight into future HSCT therapy as well as CVD pathogenesis and prevention.