Exposure to ultraviolet radiation (UVR) can result in immune suppression to antigens encountered within a few days of the irradiation. The process leading to the down-regulation in immune responses is complex. It is initiated by several photoreceptors located in the skin surface, namely DNA, trans-urocanic acid and membrane components. The absorption of UVR by these chromophores then leads to the release of a wide range of mediators that can affect antigen presenting cells locally or systemically. The final steps include the generation of antigen-specific T cells capable of regulating immunity. The consequences of the UV-induced changes in the skin immune system for the control of skin cancers, infectious diseases including vaccination, and autoimmune diseases are considered. Finally, the effects of active vitamin D, synthesised in the epidermis following UVR, are discussed in the context of the skin immune response.