Hepatobiliary dysfunction associated with the use of total parenteral nutrition is a commonly recognized phenomenon occurring in up to 90% of patients on long-term therapy. Reasons for these abnormalities, both supported by research as well as theoretical possibilities are explored. Practical guidelines considered useful in documenting, preventing and treating serious hepatic consequences of total parenteral nutrition are discussed. The role of combined liver and small bowel transplantation as treatment for select patients is also reviewed.