Glucocorticosteroids are the most potent immunosuppressive and antiinflammatory drugs. Over the six decades that have passed since their discovery, a variety of genomic effector mechanisms of steroid hormones has been described which are mediated by the cytosolic steroid receptor. Recent evidence supports a direct effect of glucocorticosteroids on cellular membranes that occurs at higher hormone concentrations, termed nongenomic effects. These imply a qualitatively distinct mode of steroid action leading to cellular apoptosis. In this review, we discuss in vitro and in vivo data on nongenomic effects of glucocorticosteroids and their possible implications for the therapy of human neuroimmunological diseases.