The metabolic response to surgical trauma is mainly characterised by an increase in BMR, a negative N balance, increased gluconeogenesis and increased synthesis of acute-phase proteins. These reactions aim at ensuring the availability of endogenous substrates for healing wounds while the synthesis of acute-phase proteins enhances the scavenging process and helps repair. However, if this process is excessive or continues for too long, it leads to a progressive depletion of body compartment with a consequent adverse outcome. Obviously, the severity of such depletion is magnified if the patient is starving or is already malnourished and the consumption of lean body mass is not compensated by an exogenous supply of nutrients. The nutritional control of this metabolic reaction represents the traditional rationale for nutritional support of surgical patients. Subsequent data have shown that the negative effects of starvation are not simply due to the starvation per se but due to the starving gut, and peri-operative enteral nutrition has proven successful in blunting the metabolic response after injury and improving protein kinetics, net balance and amino acid flux across peripheral tissue and consequently in decreasing the complications. Finally, further clinical research has shown that many post-operative infections may result from immune suppression and that such state might be reversed to some degree by modulation of the immune response through specialised nutritional support in surgical patients, regardless of their nutritional status. This paper will focus on the updated evidence-based research on peri-operative nutrition (parenteral, enteral and immune-enhancing) in patients undergoing major surgery.