Pseudo-Cushing syndromes are a heterogeneous group of disorders, including alcoholism, anorexia nervosa, visceral obesity, and depression, which share many of the clinical and biochemical features of Cushing's syndrome. The mechanisms responsible for the genesis of pseudo-Cushing's syndrome are poorly understood. It has been suggested that hypercortisolism of pseudo-Cushing syndrome may be the result of increased hypothalamic corticotrophin-releasing hormone (CRH) secretion in the context of a hypothalamic-pituitary-adrenal axis that is otherwise normally constituted. The substantial overlap in clinical and biochemical features among several patients with Cushing syndrome and those with pseudo-Cushing syndromes can make the differential diagnosis difficult. Distinguishing between pseudo-Cushing's syndrome and true Cushing's syndrome is critical for preventing the unnecessary and potentially harmful treatment of such patients. This brief review summarizes the main pathophysiological events of pseudo-Cushing syndromes and provides a useful strategy for differential diagnosis.