In this chapter are shown the advances in molecular biology and the possibilities generated by the detailed knowledge on a gene and the development of cellular and molecular methodology that enable the in vivo modification of the expression or function of a DNA fragment in particular. The powerful methods of transgenesis are described in order to study the physiological relevance of any protein. It will be shown that the transgenetic mouse and knock-out models are especially useful in the understanding of complex biological problems. The primary approaches in this chapter are to enable the non-specialist to be familiar with the techniques and restrictions of the mutagenesis in the mouse, and to describe new technologies that could overcome those restrictions. To illustrate better these items, some representative examples in the literature will be used, showing the different forms in which the genetically altered mice have been used to analyze the function of diverse organs and systems in an animal. The aim is to offer the required information to critically assess the studies in which mutant mice have been used to study biological problems and to suggest new methods to help in the biomedicine knowledge.