The incidence of skin cancer continues to increase annually despite preventative measures. Non-melanoma skin cancer affects more than 1,000,000 people in the United States every year.1 The current preventative measures, such as sunscreens and topical antioxidants, have not shown to be effective in blocking the effects of UV radiation based on these statistics. The level of antioxidants contained in the majority of skin creams is not sufficient to majorly impact free radical damage. Sunscreens absorb only a portion of UV radiation and often are not photostable. In this review article, we present the novel use of exogenous DNA repair enzymes and describe their role in combating photocarcinogenesis and photoaging. Topical application of these enzymes serves to supplement intrinsic DNA repair mechanisms. The direct repair of DNA damage by endogenous repair enzymes lessens rates of mutagenesis and strengthens the immune response to tumor cells. However, these innate mechanisms are not 100% efficient. The use of exogenous DNA repair enzymes presents a novel way to supplement intrinsic mechanisms and improve their efficacy. Several DNA repair enzymes critical to the prevention of cutaneous malignancies have been isolated and added to topical preparations designed for skin cancer prevention. These DNA repair enzymes maximize the rate of DNA repair and provide a more efficient response to carcinogenesis.