Hepatic injury is a common complication of hematopoietic stem cell transplantation (HSCT) and carries a high risk of early morbidity and mortality. Evaluation of the patient for hepatic complications should begin in the pretransplant period with the identification of pretransplant risk factors, such as hepatitis status, that may predict severe liver complications and continue through the early and late transplant periods. Early hepatic complications include drug toxicity, hepatic veno-occlusive disease (VOD), acute graft-versus-host disease (GVHD), infection, and cholestatic disorders. With increased survival of HSCT recipients, long-term liver complications from chronic viral hepatitis, chronic GVHD, and iron overload are being reported. The diagnosis and management of hepatic disorders in transplant can be complex, because one must decide whether a given symptom is due to one or a combination of diverse causes. Making the diagnosis can be crucial, because specific therapies can improve one condition but worsen another. This review describes a systematic approach to the evaluation of HSCT patients with hepatic complications with an emphasis on the need to intervene early with radiologic imaging and liver biopsy. Updated treatment options are also discussed. It is hoped that a standard approach will help to streamline clinical management of these very complex patients.