In recent years major progress has been made in identifying the molecular mechanisms by which UV radiation modulates the immune system of the skin. From these studies it appears that the generation of DNA damage and the subsequent activation of DNA repair enzymes play a critical role in the generation of UV-B-induced immunosuppression. These studies have made use of cells from both nucleotide excision repair (NER)-deficient individuals and mice. Results obtained from these studies have important clinical implications for DNA-repair-deficient patients in particular and for effective photoprotection of human skin in general.