In inflammatory rheumatic diseases such as systemic lupus erythematosus (SLE), glucocorticoids are used both as an anti-inflammatory and as immunosuppressive agents. The exact mechanisms of these general effects are complex and include alteration of both the trafficking of circulating immunocompetent cells and the actions of such cells. Thus, decreased neutrophil margination and altered peripheral lymphocyte transendothelial cell migration may be important. Similarly, modulation of the synthesis and release of inflammatory mediators and cytokines, reduction of cell surface expression of cytokine receptors and MHC class II molecules, induction of lymphocyte cell death, and modification of intracellular communication among immunocompetent cells may underlie some of the effects of glucocorticoids. These effects may represent both pharmacologic and physiologic actions. The general schema for the action of glucocorticoids involves the binding of the glucocorticoid to specific intracellular, cytoplasmic receptors in the target cell after passive movement of the steroid through the cell membrane. Corticosteroids are central to the management of SLE. The principal issue is the balance of potential risks and potential benefits, magnified by the long duration of therapy, which is usually anticipated in the management of lupus. © 2004 Elsevier Inc. All rights reserved.