A large variety of mouse models for human skin and adnexa diseases are readily available from investigators and vendors worldwide. While the skin is an obvious organ to observe lesions and their response to therapy, actually treating and monitoring progress in mice can be challenging. This chapter provides an overview on how to use the laboratory mouse as a preclinical tool to evaluate efficacy of a new compound or test potential new uses for a compound approved for use for treating an unrelated disease. Basic approaches to handling mice, applying compounds, and quantifying effects of the treatment are presented.