Mutagenesis has been the foundation of genetics in most model organisms, from prokaryotes to the fruit flies. The simplicity of mutagenizing and propagating these creatures is critical for projects designed to isolate mutations affecting most any imaginable biological process. Not only has mutagenesis been exploited for the identification of phenotypic mutants, but also for the derivation of chromosomal aberrations, such as deletions and inversions, that are powerful genetic tools for many sorts of experiments. The laboratory mouse, which serves as the most important and powerful animal model for human genetics and disease, is only recently being widely exploited by classical phenotype-driven mutagenesis. The limitation has been (and still remains) related to the biology and life cycle of the mouse, which renders large-scale mutagenesis projects rather cumbersome and expensive. Is classical chemical mutagenesis really worthwhile, given the powerful germline manipulation technologies available for mic e Are there new technologies that will render classical mutagenesis obsolete In this review, I shall discuss the tools of mutagenesis that are available for mice, and consider emerging and potential future technologies that will ultimately allow us to investigate, in an unprecedented way, the in vivo function of all mammalian genes.