Parenteral nutrition (PN) is a technique of nutritional support, which consists of intravenous administration of macronutrients (glucose, amino acids, and triglycerides), micronutrients (vitamins and trace elements), water, and electrolytes. Early studies indicate that the use of total PN was associated with increased mortality and infectious morbidity. These detrimental effects of PN were related to hyperglycemia and overfeeding at a period when PN was administered according to the principle that the higher calories the patients received, the better their outcome would be. Enteral nutrition (EN) then replaced PN as the gold standard of nutritional care in the intensive care unit (ICU). However, EN alone is frequently associated with insufficient energy coverage, and subsequent protein-energy deficit is correlated with a worse clinical outcome. Infectious and metabolic complications of PN could be prevented if PN is used by a trained team using a validated protocol, only when indicated, not within the first 2 days following ICU admission, and limited through the time. In addition, energy delivery has to be matched to the energy target, and adapted glucose control should be obtained. In patients with significant energy deficit (>40%), the combination of PN and EN, i.e. supplemental PN, from day 4 of the ICU stay, could improve the clinical outcome of ICU patients as compared with EN alone. Therefore, PN should be integrated in the management of ICU patients with the aim of prevent the worsening of energy deficits, allowing the preservation of lean body mass loss, and reducing the risk of undernutrition-related complications.