Melanoma constitutes 4-5% of all skin cancers but it contributes to 71-80% of skin cancer deaths. UV light affects cell and tissue homeostasis owing to its damaging effects on DNA integrity and modification of expression of a plethora of genes. DNA repair systems protect cells from UV-induced lesions. Several animal models of melanoma have been developed (Xiphophorus, opossum Monodelphis domestica, mouse models and human skin engrafts into other animals). This review discusses possible links between UV and genes significantly related a melanoma, but does not discuss melanoma genetics. These include oncogenes, tumor suppressor genes, genes related to melanocyte-keratinocyte and melanocyte-matrix interactions, growth factors and their receptors, corticotropin-releasing hormone, adrenocorticotropic hormone, α-melanocyte-stimulating hormone, glucocorticoids, inhibitor of DNA binding 1, nuclear factor-κB and vitamin D3. © 2007 Future Drugs Ltd.