Acute and prolonged illness seems to result in a variety of different neuroendocrine alterations. During the acute phase of critical illness there is an actively secreting anterior pituitary gland and a peripheral resistance to anabolic hormones. In the chronic phase of critical illness there is a uniformly reduced secretion of anterior pituitary hormones, with the notable exception of cortisol. The main characteristic of these alterations is the ‘wasting’ syndrome. An acute event, such as an infection or emergency surgery in a long-stay ICU patient, is accompanied by mixed acute/chronic endocrine patterns. Wasting syndrome is manifested, among others, with hyperglycemia and insulin resistance, while the severity of this ‘diabetes of stress’ reflects the risk of death. Recently it was shown that preventing these metabolic patterns with insulin infusion improves outcome in critically ill patients. It remains to be demonstrated if other endocrine interventions will accelerate recovery, especially in long-stay patients in ICU.