Technical advances in the generation of genetically modified (GM) mice and the efforts of large-scale consortia have provided a wealth of resources to the biomedical research community. It has never been easier to obtain a specifically modified allele. However, the establishment and production of GM mouse models using basic breeding methods can still present a unique set of challenges. This chapter aims to equip those new to mouse colony management with some valuable tools. Topics covered include basic reproduction and inheritance, welfare assessment, nomenclature, breeding schemes, and calculators for the production of desired genotypes. Breeding of transgenic founders or chimeras through the first generations is discussed as well as the influence of strain background on this process. Animal records management systems also play an important role in effective colony management.