Acute and chronic stress as well as a number of psychiatric and neurological disorders are accompanied by profound disturbances of the HPA system. These neuroendocrine alterations act back on the central nervous tissue mainly via corticosteroids-affecting glucocorticoid and mineralocorticoid receptors. The major conclusions drawn from studies probing these receptors in clinical investigations are: (1) In many such conditions central corticosteroid receptors are weakened in their capacity to curtail spontaneous and stress-elevated corticosteroid levels; (2) the combined DEX-CRH test is the best neuroendocrine tool currently available for identifying HPA abnormalities in psychiatric patients; (3) in depression the decreased corticosteroid receptor capacity in transient, and antidepressants act through reinstatement of GR and MR function probably resulting in reduced hypothalamic CRH and AVP production; (4) several neurological disorders such as MS and HIV infection are often accompanied by altered HPA function, which has therapeutic implications; and (5) various corticosteroids, their biosynthetic precursors and their metabolites have differentiable effects on the sleep EEG, which can be attributed to their mode of action; specifically, steroids such as pregnenolone and DHEA most likely are produced in glia cells and act in a paracrine fashion at neurons, thus modifying the sleep EEG in humans in a manner that suggests their potential as memory enhancers.