Recommendations for nutritional support in critically ill patients differ in a variety of attributes. The optimal amount of calories and nutritional substrates supplied necessary for reducing morbidity and mortality has been suggested, but is not well established due to the complexity and variation in the underlying clinical conditions of each patient. This chapter summarizes pertinent information concerning the nutritional support of critically ill patients in the intensive care unit (ICU) with regard to energy, protein, carbohydrate, and lipid provision and their impact on morbidity and mortality. Enteral nutrition (EN) is generally advised over parenteral nutrition (PN) and is helpful when administered within 24–48 h of admission to the ICU. Conversely, early provision of PN does not provide significant advantages in terms of improving morbidity and mortality, and the best time to initiation remains unclear. The administration of a hypocaloric (<20 kcal/kg/day), high-protein diet (e.g., amino acid doses of ≥2 g/kg/day), during the first week of critical illness, appears to be the most beneficial recommendation. Another important consideration for minimizing morbidity is maintenance of glycemic control with blood glucose concentrations of 120–150 mg/dL, which can be achieved through the use of insulin and decreased doses of dextrose (i.e., 1–2 g/kg/day). Intravenous lipid emulsions (ILEs) are also used as a fat source to meet energy requirements because insulin resistance is present in many patients and to prevent essential fatty acid deficiency. Micronutrient needs will also vary in response to the extent of inflammation present. An individualized approach is best.