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Breakdown of gut barrier defenses, dysbiosis of intestinal microbiota, and exaggerated immune responses dictate that early enteral nutrition (EN) is preferred over parenteral nutrition (PN) as the primary route of nutrition therapy. EN, however, is not feasible in all cases because of intolerance, risk of complications, or a direct contraindication to enteral feeding. For these patients, PN can be provided in a manner that is safe, is metabolically appropriate, and follows the principles of modern critical care nutrition. Adherence to goal\u2010directed fluid resuscitation, provision of trophic doses of PN to meet 20%\u201325% of protein and\/or calorie requirements through the acute phases of illness, use of less\u2010inflammatory intravenous lipid emulsions, and close monitoring of electrolytes, triglyceride levels, and signs of refeeding syndrome all serve to optimize the response to this route of nutrition support. 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