Cutaneous cancers represent a major public health concern due to the very high incidence, associated medical costs, substantial mortality, and cosmetic deformities associated with treatment. Considerable progress in basic research has provided new insights into the underlying genetic basis of the major human cutaneous cancers, malignant melanoma, basal cell carcinoma, and squamous cell carcinoma. In turn, these genetic insights have illuminated biochemical pathways that promise to provide new approaches to the prevention and treatment of cutaneous neoplasms. This review will detail the evolving genetic information and indicate how this information is being used to refine experimental models that serve to both define the biochemistry of cancer pathogenesis and test novel approaches to cancer therapy. Combined with preventive measures to reduce exposure to sunlight, these advances are likely to reduce this major public health burden in the coming decade.