The ability to specifically manipulate gene expression in vivo using mouse models has been one of the most important advances in understanding gene function over the last few decades. Methods used to control gene activities in the mouse include gene targeting and transgenic approaches. While gene targeting methods have proven to be powerful genetic tools designed to eliminate gene function by creating a "knockout" or "null mutant," transgenic studies offer gain-of-function capabilities, expression of dominant negative or knockdown of specific target genes and thus have often served a complementary and useful role. This chapter provides an overview for the generation of transgenic mouse models to study important questions in skin biology by taking advantage of the tetracycline-inducible gene expression system.