The establishment of novel animal models using gene targeting and transgenic technology has opened a new area of neuropharmacological research. For the first time, it became possible to alter the expression of a gene in a specific cell type of an intact animal by either overexpression, inhibition or ablation. This review describes the technology and lists the relevant tools, such as reporter genes, suicide genes, immortalizing genes, and promoters, necessary for the targeted expression of these and other genes in specific cells of the central nervous system. In addition, the problem is discussed that the mouse is the species in which this technology is by far the most developed, while the rat has been used as the model species for neuropharmacology during the last century.