Since their introduction, the extraordinary importance of glucocorticoids in the treatment of inflammatory and autoimmune disorders is undisputed, despite their known undesirable side effects. In the 1990s, major scientific progress was made, with the discovery that positive and negative regulation of gene expression via the glucocorticoid receptor are mediated by different mechanisms. This discovery led to the assumption that it may be possible to dissociate the therapeutic effects of glucocorticoids from their side effects by using ligands which specifically or preferentially address one of the two pathways. Several pharmaceutical companies are currently pursuing this goal.