The more knowledge accumulates on the molecular action of glucocorticoids, the less appears to be known about the physiological relevance of these data. Mechanisms that determine bioactivity of glucocorticoids are largely neglected in studies on their molecular actions in immunoregulation. However, alterations of these mechanisms may contribute to the pathogenesis of acute of chronic inflammation, ranging from septic shock to autoimmune disease, or even acquired immuno deficiency syndrome. In this article, Thomas Wilckens attempts to challenge the long-standing dogma of glucocorticoids being only immunosuppressive in their action, and suggests a physiological role in which they are a prerequisite for a coordinated immune response.