Cross-talk between different transcription factors, notably between the glucocorticoid receptor and AP-1, has been discovered more than 10 years ago: a bona fide transcription factor, without apparent need for its own direct DNA contact, influences the activity of another transcription factor. Recent experiments have added interesting aspects: in addition to major insights into the mechanism of cross-talk, it is now clear that the cross-talk ability of glucocorticoid receptor is essential for mouse development, while the activation of target promoters carrying a glucocorticoid response element (GRE), is surprisingly, dispensable for survival under animal house conditions. Interestingly, the cross-talk function is responsible for almost all regulatory actions of cortisol in the immune system. It is possible that the two functions of the glucocorticoid receptor can be activated separately by specific ligands. Future goals will be to define whether adverse effects of long-term corticosteroid treatment, e.g. osteoporosis, joint necroses, metabolic effects, can be ascribed to GRE-target gene activation and thus be dissociated from the desirable actions in the treatment e.g. of autoimmune disease.