Many cancers are the pathological consequence of environmentally initiated disruptions to cellular genetic control mechanisms. For most cancers the relevant environmental carcinogens have not been identified, but one major exception is cutaneous malignant melanoma, for which the primary environmental agent is solar ultraviolet (UV) radiation. Hence, melanomagenesis represents a potential model of detrimental gene–environment interaction. Although the underlying genetic basis of melanoma is currently being elucidated, fundamental questions concerning UV and the mechanisms by which it operates remain unanswered. Significant progress has recently been made in creating UV-responsive, genetically tractable mouse models of melanoma that accurately recapitulate human disease. These models are providing novel insights into how the genome and environment interact in vivo.