Recent advances in genetic approaches significantly extended horizon of opportunities to manipulate with expression of mammalian genes in vivo resulting in development of thousands of mouse strains carrying specific genetic alterations. Microdialysis shows a great utility to analyze consequences of such genetic manipulations on the processes governing synthesis, release, uptake, and neurotransmitter interactions in a physiologically or behaviorally relevant context. In this review, a history of microdialysis in mutant animals, practical considerations of microdialysis applications in mouse genetic models, and several examples of such applications are discussed. With the increasing power and fidelity of genetic manipulations and the development of uncountable number of various mutant mice, an explosion of studies using microdialysis in genetic models could be expected.