Abstract: Liver injury is associated with parenteral nutrition therapy. Severity of injury varies from minimal and transient increases in liver-related blood tests to biliary cirrhosis and liver failure. Severe parenteral nutrition-related liver disease is usually confined to patients who have undergone massive intestinal resection. In these patients, early sepsis appears to cause initial liver injury, and recurring sepsis and inflammation, local or systemic, may result in its perpetuation and progression. Liver disease associated with parenteral nutrition is not necessarily related either to duration of parenteral nutrition or to delayed intestinal feeding. However, treatment includes enteral nutrition to promote enterohepatic circulation of bile acids and management of inflammation and sepsis, including control of intestinal bacterial overgrowth. Restriction of intravenous lipid emulsions may be important. The clinical picture of advanced liver failure related to short bowel syndrome differs from liver failure with an anatomically normal gastrointestinal tract. In the former, hyperbilirubinemia, hepatosplenomegaly, and functional hypersplenism dominate the clinical picture, and severe ascites and esophageal variceal hemorrhage are unusual. Early referral of these patients for intestinal and/or liver transplantation may provide the best chance for long-term survival.