Transgenic mice are a beneficial tool that can allow researchers to investigate the roles of specific genes in physiology and disease. However, conventional transgenic mice have the limitation that constitutive expression of a transgene from the embryonic stage may affect the normal development of the mice or cause compensating effects. To overcome these disadvantages, tetracycline-controlled transgenic mice, which can express target gene products in a tissue-specific and time-dependent manner, have been developed. In this section, the principles of tetracycline-controlled systems are discussed first. In addition, useful information for generating transgenic mice using this system is introduced.