At present, ultraviolet radiation (UVR) represents one of the most important environmental factors affecting mankind. Besides the beneficial effects of UVR such as vitamin D production, it is known that UVR can lead to adverse effects on human health. The best known harmful effects are sunburns, tumors of the skin and ocular damage. It is noteworthy that UVR effects are not restricted to skin-associated infections, as there is strong evidence for their association with systemic (non-skin-associated) infections as well. Alterations in immune functions that are induced by UVR are initiated by the absorption off light energy by chromophores and their transformation into photoproducts. Some of them are removed by repair mechanisms; others induce signal transduction pathways, whereas some exhibit cytotoxicity. The observable skin response may occur within minutes of light exposure (e.g. urticaria) or may take days (e.g. inhibition of contact hypersensitivity), or much longer periods to be expressed (e.g. tumors). Today, artificial UVR (phototherapy) is used in dermatology for induction of immunomodulation in many forms of autoimmune and/or hyperimmune responses in the skin.