The catabolic state of prolonged critical illness is associated with a low activity of anterior pituitary functions. Before considering endocrine intervention in these conditions, a detailed understanding of the neuroendocrinology of the stress response is warranted. It is now clear that the acute phase and the later phase of critical illness behave differently from an endocrinological point of view. When the disease process becomes prolonged, there is a uniformly-reduced pulsatile secretion of anterior pituitary hormones with proportionally reduced concentrations of peripheral anabolic hormones. Apparently, there is a constant interaction between neuroendocrine and internal immunoregulatory mechanisms that assures the fine tuning of both the neuro-endocrine and the immune system, so that both are able to preserve homeostasis of patients during severe and life-threatening illnesses.