Neuropsychiatric disorders often involve considerable psychological stress and elevated cortisol activity. Glucocorticoid receptors have relatively low affinity for cortisol and are found distributed throughout the brain, particularly in the frontal cortex and hippocampus. In recent years, glucocorticoid receptors antagonists have been actively studied in both animal models of several disorders as well as a potential treatment in specific types of neuropsychiatric patients. Data from these various studies are reviewed with an emphasis on seven clinical disorders or problems: major depression with psychotic features, bipolar disorder, schizophrenia, cognitive disorders, (e.g., Alzheimer's disease and mild cognitive impairment), cognitive side effects of electroconvulsive therapy, and weight gain with atypical antipsychotic agents. Potential benefits and limitations are discussed.