The skin, because of its privileged site, is continuously exposed to a number of potentially injurious stimulae, not encountered in other organs. In much the same way that mucosal structures, such as the gastro-intestinal tract, have developed specialised immunological responses directed to its special needs, for example the production of secretory IgA and mucosal homing T lymphocytes, so the skin has its own specialised structures. Critical amongst these are epidermal antigen presenting Langerhans cells, which form a network throughout the epidermis, and skin homing lymphocytes. Keratinocytes also critically influence skin immune responses and should therefore be considered as specialised immunologically active cells. To reflect the growing evidence for an active immunological role for the skin, Bos coined the term Skin Immune System (SIS), building on skin associated lymphoid tissue (SALT) defined by Streilein (1), to define the multiple cell types and the complexity of immune responses within the skin (2).