Critically ill patients with systemic inflammatory response syndrome (SIRS) and multi-organ failure are at great risk of nosocomial infections due to a reduced immune status. There is growing evidence from in vitro studies and animal models that the reduced immune response might be improved by the so-called immunomodulatory nutrition. Based on these studies there are now some commercially available enteral or parenteral solutions with immunomodulatory substrates, such as n-3 polyunsaturated fatty acids (PUFAs), arginine and nucleotides. Recently, enteral nutrition with this experimental formula reduced the hospital length of stay and the frequency of acquired infections in critically ill patients. The increasing knowledge about the metabolic effects of these nutritions offers therapeutic potential for the future, and might reduce the mortality of critically ill patients from nosocomial infections. However, at present, studies are necessary to find the best time for beginning and duration of the feeding. In addition, the optimal dosage and composition of these pharmacologically active substances has to be investigated.