As sunscreens do not provide complete protection against solar/UV radiation, alternative protective strategies are necessary to cope with the increasing incidence of skin cancer. These strategies include the reduction of UVR-induced DNA damage by the topical application of bacterial DNA repair enzymes. Recent evidence suggests that nucleotide excision repair, the physiological repair system that is mostly responsible for the removal of UVR-mediated DNA damage, can be modulated by cytokines, including IL-12, IL-18, and alpha-melanocyte-stimulating hormone. The mechanisms involved and the biological as well as the potential therapeutic implications of these findings are discussed.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 63-66; doi:10.1038/jidsymp.2009.3.