Infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) are associated with significant morbidity and mortality among patients with cancer, especially in patients with hematologic malignancies and those who undergo hematopoietic stem-cell transplantation. Reported rates of HBV reactivation in HBV carriers who undergo chemotherapy range from 14-72%. In these patients, mortality rates range from 5-52%. HCV reactivation seems to be less common than HBV reactivation and is usually associated with a good outcome and low mortality. However, once severe hepatitis develops, as a result of viral reactivation, mortality rates seem to be similar among patients infected with HBV or HCV. Liver damage owing to viral reactivation frequently leads to modifications or interruptions of chemotherapy, which can negatively affect patients' clinical outcome. Risk factors for the development of severe HBV or HCV reactivation need to be better defined to permit identification of patients who may benefit from preventive measures, early diagnosis, and therapy. In this article, we review the epidemiology, pathogenesis, risk factors, and clinical and laboratory manifestations associated with reactivation of HBV and HCV during immunosuppressive therapy. We also discuss strategies for the prevention and treatment of viral reactivation, including the management of reactivation with new antiviral agents.