It is accepted that nutrition support is essential in the treatment of critically ill patients. It is also reasonable to initiate nutrition support therapy as soon as possible. Although malnutrition is most frequently associated with a risk for immune dysfunction, it can affect all organ systems. Thus, ICU patients are in need of immunonutrients supplementation. An additional strategy to maximize the benefits is to consider using products supplemented with specific nutrients that modulate the immune system, improve wound healing, and reduce oxidative stress. The lower incidence of infectious complications may follow in shorter lengths of both intensive care units (ICU) and hospital stays. Many studies have concentrated on nutrients to stimulate the function of cellular immunity in these patients. These nutrients include arginine, glutamine and omega-3 fatty acid which has direct effect on T lymphocytes and macrophage. Enteral formulas designed as immune-enhancing diets (IED) contain supplemental amounts of L-arginine, L-glutamine, nucleotides and the long chain polyunsaturated fatty acids: eicosapentaenoic acid (EPA), docosahexanoic acid (DHA) and arachidonic acid (ARA) in addition to nutrient substrates essential for general nutrition and metabolism. These formulas vary considerably in composition of these four primary substrates. They introduce the immune cell function augmentation, inflammation regulation and infections minimization. Glutamine, a conditional-essential amino acid, an essential energy source, a precursor for protein synthesis and donates nitrogen for the synthesis of purines, pyrimidines, nucleotides, amino sugars, and glutathione antioxidant.