One of the more controversial areas in critical care in recent decades relates to the issue of adrenal insufficiency and its treatment in critically ill patients. There is no consensus on which patients to test for adrenal insufficiency, which tests to use and how to interpret them, whether to use corticosteroids, and, if so, who to treat and with what dose. This review illustrates the complexity and diversity of pathophysiological changes in glucocorticoid secretion, metabolism, and action and how these are affected by various types of illness. It will review adrenal function testing and give guidance on corticosteroid replacement regimens based on current published literature. There remain inherent difficulties in interpreting the effects of glucocorticoid replacement during critical illness because of the diversity of effects of glucocorticoids on various tissues. Investigation and treatment will depend on whether the likely cause of corticosteroid insufficiency is adrenal or central in origin.