Parenteral nutrition is a life-saving treatment for patients who have acute and chronic intestinal failure. Severe cholestasis induced by total parental nutrition (TPN-IC) is characterized by bile duct regeneration, portal inflammation, and fibrosis. Its progression could be very rapid, and in some patients liver cirrhosis may develop in few months. This article describes the definition, incidence, hepatic changes, histopathologic findings, risk factors, pathogenesis, and clinical implications of TPN-IC. The goal is to improve hospital and home management, quality of life, and prognosis of patients requiring parenteral nutrition.