The first generation of genetic mutations in mice, conventional transgenics and knockouts, have provided important new insights into many aspects of brain function, including complex behavior. Moreover, as genetic variants that contribute to the development of mental disorders are found, mice bearing these genes represent novel and powerful animal models of the disorders. However, these mutations are complicated by the fact that they generally occur at early stages of development and in many and perhaps most tissues of the body. This complicates the use of these mice for studies of gene function in adult organisms. The last five years has seen the development of second generation mutations in mice, in which the mutation (either loss or addition of a gene) can be controlled temporally and spatially, that is, the mutation can be induced in adult animals and targeted to a particular brain region and neuronal cell type. Although not yet routine, such inducible and cell-type specific mutations represent powerful new tools to understand the role of a particular gene in complex behavior.