Many members of the nuclear receptor (NR) superfamily are expressed in the skin making them a highly interesting subject of dermato-endocrine research. Natural and synthetic NR ligands are used for the treatment of various skin disorders. We discuss here the impact of the dynamic nature of chromatin organization, i.e., the spatio-temporal changes of chromatin region of NR target genes. This dynamics is triggered by environmental changes, of which for NRs the exposure with their ligands is most critical. For an understanding of skin disorders, which involve the actions of NRs, this means that the parameter time should be carefully considered in context of other factors that may influence the chromatin organization, and by this the responsiveness, of key NR target genes.