The knockout mouse is one of the most useful experimental animal systems in which to clarify functions of identified genes in vivo. Numerous knockout mice have been produced, and studies in these models have revealed new aspects in various biological fields. In fair cases, however, mice died during embryogenesis due to complete gene disruption, making it difficult to elucidate functions of given genes in adulthood. To avoid this, conditional gene targeting has been performed and shown to be effective on numerous cases. Here, we will overview established strategies for conditional gene targeting and present the results of our recent studies using the Cre/loxP system in the skin.