ESSENTIAL POINTSThe daily rhythmicity of plasma glucocorticoid (GC) levels is a strong modulator of many physiological and psychological processes, although its functional significance is poorly understood.The suprachiasmic nuclei of the hypothalamus have been shown to harbor a molecular clock mechanism generating circadian rhythmicity in mammals, but the same mechanism is present in many peripheral tissues and elsewhere in the brain.Mineralocorticoid receptors and glucocorticoid receptors mediate the action of naturally occurring GC in complementary fashion.Optimal physiological effects of GC occur when the central signal that controls the rhythm of GC release and the peripheral rhythms in tissues expressing GC receptors are aligned.New studies suggest that misalignment of central and peripheral oscillators may increase the risk of disease, with adverse effects on the immune system, cardiovascular system and metabolism, among others prominent.Chronopharmacological strategies that attempt to normalize the rhythm of circulating GCs have potential to improve the treatment of a wide variety of physical and mental conditions.