Cytokines, hormones and other signaling molecules regulate a number of diverse biological processes in the skin including the control of cell growth, differentiation, homeostasis, and various immune functions. This review describes the fundamental concepts of signaling in the cell and we discuss more thoroughly selected signaling pathways important in the skin. Fundamentally cellular signaling can be mediated through two different signaling mechanisms: 1) through binding to a receptor at the outer surface of the cellular-membrane and a subsequent activation of a signal transduction cascade. 2) through binding to nuclear receptors and subsequent regulation of gene-transcription. Changes in the signaling apparatus in the cell play a key role in the pathogenesis of a number of different skin diseases and a better understanding of these different signaling pathways may therefore offer new therapeutic targets.