Cushing's syndrome (CS) is a relevant model to better understand the effects of glucocorticoid (GC) excess on the human brain. The importance of GC excess on the central nervous system is highlighted by the high prevalence of neuropsychiatric disorders such as depression and cognitive impairment in patients who have CS. In addition, there is a high incidence of apparent diffuse loss of brain volume in patients who have CS. Recent studies indicate at least partial reversibility of these abnormalities following correction of hypercortisolism.