After antigenic stimulation the increase in cytokine levels constitutes a fundamental event in the host defense and mediates many processes such as inflammation, B- and T-cell growth and differentiation and activation of effector cells. Most of these processes depend on the cytokine-induced activation of transcription factors that modulate the expression of target genes. Cytokines induce a rise in glucocorticoid levels, which are instrumental in controlling immune-cytokine overreactions. Because of their anti-inflammatory and immunosuppressive actions, glucocorticoids are highly useful as therapeutic drugs in a range of diseases. The cross-talk between cytokine-induced transcription factors such as nuclear factor-kappaB, activating protein-1, cAMP responsive element binding protein and nuclear factor of activated T cells, and glucocorticoid receptors involves both genomic and non-genomic actions, and constitutes the mechanism by which glucocorticoid repressive effects on cytokine synthesis and action take place. These molecular interactions represent the key for the study of physiological compensatory actions of corticosteroids, the interactions of cytokines and glucocorticoids at their target cells, as well as the therapeutic benefits and side-effects of synthetic steroids. For this reason, we will focus on the molecular aspects of cytokine-glucocorticoid interactions, represented by the cross-coupling between cytokine-mediated transcription factors and glucocorticoid receptors.