The response to surgical injury is mediated through the hypothalamus and is characterised by the release of catecholamines, glucocorticoids, growth hormone and glucagon; the suppression of insulin secretion and changes in other endocrine systems. These hormonal responses trigger a cascade of metabolic adjustments leading to catabolism and substrate mobilization in the postoperative period. There is evidence that a severe and prolonged catabolic reaction to injury may be associated with an increased morbidity and mortality in high-risk adult patients. This article reviews the historical background of investigation in this field, together with recent advances in the understanding of the complex metabolic phenomena following surgery. These changes are discussed with particular reference to therapeutic manipulation of the stress response using anaesthetic, hormonal or nutrition regimens. It is concluded that further research in this field may provide major clinical benefits in the management of critically ill patients undergoing surgical stress.