The mechanisms underlying UV-induced immunosuppression and the development of UV-induced skin cancer have been intensively investigated for decades. In particular, UV-induced DNA damage and UV-induced suppression of cellular immune responses were analyzed in great detail. During this time, several cellular and genetic pathways were identified, that are involved in photoimmunology and photocarcinogenesis. However, the direct effects of the complex UV-induced pathways on immunosuppression or on cutaneous tumor generation in vivo have not been able to be characterized with certainty so far. With the increasing availability of mutant mice that lack or overexpress certain genes, more information can be obtained with respect to the functional importance of individual gene products and the signaling pathways involved in UV-mediated immunomodulation and cancer development. This article is an overview of the results of UV-induced immunosuppression and photocarcinogenesis experiments obtained in different mutant mice.