The emergence of techniques that allow fine manipulation of gene expression in the mouse have changed the way biomedically relevant processes are studied, as they allow their analysis in the living animal. In addition, this has opened the possibility to generate animal models for several human diseases, which are useful both for understanding the disease's physiopathological mechanisms and for the eventual evaluation of novel therapeutic approaches. Many of the gene manipulation systems currently employed in the mouse are based on regulatory mechanisms normally operating in yeast and prokaryotic organisms. This has allowed specific experimental control with very limited unspecific interference with the normal physiology of the cell. Some of these systems use elements that permit transcriptional regulation of a particular gene or genes. Among them, I will discuss in detail the tet, lac and Gal4/UAS systems, which are among the most popular of these transcriptional systems because they can be used to achieve spatial and temporal control on the expression of a specific gene in a reversible fashion. The other major group of systems currently employed to manipulate gene expression in the mouse is based on site-specific recombination reactions. The Cre/lox and FLP/FRT systems are the most popular of these. I will discuss how these recombination systems are used in the mouse with special focus on their use to achieve specific gene activation.