Few other organs have the environmental exposure-neoplasia relationship that has been observed between epithelial cutaneous malignancy and UVB exposure. A significant DNA type of defective linking of DNA nucleotides involves pyrimidine dimers. Important insight into the molecular processes that affect the response of cells to UVB have been provided by the study of rare inherited diseases characterized by DNA repair defects. Nucleotide excision repair is the best characterized of these and its importance is illustrated by the disease, xeroderma pigmentosum. This heterogenous disorder clinically characterized by malignant tumor development and molecularly by distinct alterations in the nucleotide excision repair apparatus. More recently, other DNA mechanisms have been shown to have some role in skin cancer, such as DNA-mismatch repair and double-stranded DNA breaks. Herein, we discuss the DNA-repair adjuvants a aqueous extract of Urcaria tomentosa (AC-11, Optigenex, Inc.), and T4 endonuclease V that is prepared in a liposome lotion (Dimericine, Applied Genetics Inc. Dermatics). The positive effects on the integrity DNA of other substances (from nature, heat shock proteins and cytokines) including IL-12, Polypodium leucotomos, and ubiquitin are also reviewed. Understanding DNA repair mechanisms is far from complete; further understanding will provide insight into the pathogenesis of cancer and pave the way for efficacious therapeutic agents.