Loss of body protein?mostly from skeletal muscles?is the most characteristic sign of critical illness. The most common immune-enhancing nutrients for favorable Compensatory Anti-inflammatory Response Syndrome (CARS) are glutamine, arginine, poly-unsaturated fatty acid, some trace elements and probiotics. Glutamine is an essential amino acid with an important role it fuels the proliferation of cells and acts as a precursor to antioxidant glutathione. The conflicting results of glutamine trials are largely related to its dosage and duration of treatment. However, its overall effects, when parenterally or enterally supplied, are thought to be helpful in immune-enhancing and decreasing infectious complications. Arginine is also conditionally essential and has an important role in the synthesis of anabolic hormones and in the activation of T lymphocytes. It also is converted to citrulline and nitric oxide, the latter is a potent intracellular signaling molecule. Leucine and citrulline are common in the mechanism of action and are mediated by the mTOR signaling pathway. Both leucine- and citrulline-enriched diets have been proven to increase nutritional status in various experimental models of injury. However, there are conflicting data about when they were supplied to the critically ill patients. The role of the most immune-modulating nutrients have not been fully discovered thus far. For critically ill patients, basic support with macro-nutrients should come first, followed by other specially provided nutrients, such as immunonutrients.