In critically ill patients, the hypothalamic-pituitary-adrenal axis is usually activated, resulting in elevated plasma cortisol levels. This enables the human organism to cope with sepsis, trauma and other forms of stress. During critical illness, total adrenal insufficiency rarely occurs. On the other hand, septic shock can be accompanied by a relative deficit of cortisol. Causes of this relative adrenal insufficiency are a dysfunction of the hypothalamic-pituitary-adrenal axis and/or cortisol resistance. There are no strict biochemical criteria available to diagnose relative adrenal insufficiency; clinical observation is the decisive factor. In randomised trials with patients in septic shock, a more rapid haemodynamic recovery was obtained with physiological doses of hydrocortisone than with a placebo. The observed haemodynamic response following hydrocortisone administration supports the concept of relative adrenal insufficiency.