This article presents a comprehensive overview of the physiological, cellular, biochemical, and molecular actions of glucocorticoids. Emphasis is placed on the structure of the glucocorticoid receptor, the process known as receptor activation, and the function of endogenous regulators in receptor-mediated signal transduction. The role of receptor phosphorylation, and the activities of exogenous sodium molybdate, are also reviewed. In addition, recent advances in the structure and mechanism of action for the low mol wt heat-stable "modulator" of glucocorticoid receptor activity are also discussed. Modulator is a novel ether aminophosphoglyceride that appears to be the "endogenous molybdate factor." A model is presented for the interaction of modulator with the glucocorticoid receptor. This model seeks to explain the actions of sodium molybdate toward the glucocorticoid receptor, and perhaps toward other steroid-hormone receptors as well. Finally, results from an ultra-large scale purification of two new modulator isoforms, and the activities of these isoforms toward the glucocorticoid receptor, the mineralocorticoid receptor, and protein kinase C, are also summarized.