The skin, our body's largest organ, is located at the interface between the external and internal environments, and so is strategically placed to provide not only a barrier against a range of noxious stressors (UV radiation, mechanical, chemical and biological insults) but also to act as the periphery's 'sensing' system. Recent developments suggest that this organ is much more critical to maintaining body homeostasis than previously thought. This tutorial review introduces the reader to some of the biochemistry that underpins the skin's enormous multi-functionality.