Patients undergoing major surgery are at increased risk of developing post-operative complications. In the last years, several clinical studies and meta-analyses focused on the potential clinical benefits of perioperative immunonutrition in surgical patients and showed contradictory results with regard to complications. The aim of this study is to summarize the concept of immunonutrition and the results of those clinical trials and to draw recommendations about the current indications of immunonutrition in surgery. A range of nutrients, including several amino acids, antioxidant vitamins and minerals, long-chain n-3 fatty acids, and nucleotides have been shown to upregulate the host immune function, modulate inflammatory response, and improve gut barrier function after surgery. Several experimental studies have been carried out that support potential benefits of these nutrients in the surgical patients. The majority of the randomized trials found that perioperative immunonutrition improved short-term outcomes in patients who underwent elective major gastrointestinal (GI) surgery. Five meta-analyses including a large number of randomized clinical trials showed that perioperative immunonutrition is associated with a reduction in both the infection rate and the length of hospital stay. These results have been demonstrated in all patients undergoing both the upper and lower GI surgery, regardless of their baseline nutritional status. Promising results have been obtained also in head and neck surgery. Considering these findings, perioperative immunonutrition should be implemented in patients undergoing elective major GI surgery. The use of perioperative immunonutrition could reduce both postoperative morbidity and costs for healthcare systems. However, large- scale trials are required before recommending the routine use of immunonutrition in head and neck surgery. (JKSPEN 2013; 5(1):10-14)