The skin is equipped with nerve fibers subserving the senses for touch, temperature, pain and itch. Thickly myelinated Aβ-fibers are linked to low threshold mechano-receptors responsible to detect vibration and slight indentation of the skin. Among the thinly myelinated Aδ-fibers one class is crucial for the cold detection, but there also nociceptive Aδ-fibers for the detection fast rising noxious heat and punctate mechanical stimuli. Unmyelinated C-fibers consist of various classes mediating nociceptive (pain and itch) and non-nociceptive (warmth, pleasant touch) sensations. The unmyelinated C-fibers have close contact to the keratinocytes and the interaction between C-fibers and local skin cells is of particular interest, as efferent neuronal function has both local trophic and immunomodulatory function. In turn, excitability of C-fibers is governed in part by neurotrophins from neighbouring skin cells such as keratinocytes. This mechanism is held responsible to induce and maintain chronic itch and pain conditions. Beyond this interaction recently a direct involvement of keratinocytes in the transduction process has been discussed especially for temperature and noxious stimuli, as keratinocytes express a variety of sensory transduction molecules. Thus, the interplay between neurons and non-neuronal cells is operational not only in basic physiology, but also in chronic itch and pain patients.