Ultraviolet (UV) radiation can exert a variety of biological effects, including induction of skin cancer, premature skin ageing and inhibition of the immune system. The immunosuppressive properties of UV radiation are of major biological and clinical relevance since suppression of the immune system by UV radiation also contributes to the induction of skin cancer. Hence, understanding of the mechanisms by which UV radiation compromises the immune system is of primary importance. UV radiation suppresses the immune system in multiple ways. It inhibits antigen presentation, stimulates the release of immunosuppressive cytokines and induces the generation of lymphocytes of the regulatory subtype. The major molecular target for UV-induced immunosuppression is UV-induced DNA damage. Further elucidation of the mechanisms underlying UV-induced immunosuppression will not only lead to a better understanding of the physiologic and pathologic effects of UV radiation but also contribute to the development of new protective strategies.