Critical illness evoked by trauma, extensive surgery, or severe medical illnesses is the ultimate example of acute severe physical stress. The endocrine response in a critically injured and stressed patient is varied and complex. Although the acute and chronic phases of critical illness are characterized by distinct endocrine responses, the diagnosis of these disorders is controversial. The inability to define the endocrine change as either adaptation or pathology renders the issue of treatment even more controversial. In addition, patients may have preexisting endocrine diseases, either previously diagnosed or unknown, and hence endocrine evaluation in a critically ill patient poses a major challenge to the health care provider. This review provides a novel insight into the dynamic endocrine alterations that occur during evolution of stress hyperglycemia and adrenal insufficiency in the critically ill patient and the available evidence for the therapy of these disorders.