Anti-inflammatory treatment of eczematous skin diseases like atopic dermatitis and allergic contact dermatitis has mainly been performed with topical glucocorticosteroids. Increasing knowledge of the pathophysiological interactions and the immunological mechanisms during the chronic inflammatory processes in the skin offers new therapeutical options. In this review, new therapeutical approaches for the treatment of eczematous skin disease will be presented. These novel compounds include the topical immunomodulators, tacrolimus and pimecrolimus. Such molecules inhibit intracellular signal transducing phosphatases and act consecutively at the molecular level by inhibiting the activation of transcription factors. Secondly, the development of nuclear hormone receptor family members, such as retinoids, vitamin D and peroxisome proliferator-activated receptor agonists, is discussed. Substances from this family have differentiating, antiproliferative, but also immuno-modulatory effects, which make them attractive as anti-eczematous therapeutic compounds. The diversity of these interactions is extensive, and clinical studies will prove their clinical efficacy.