Genetically modified mice are mainstream tools for medical research. The background strains used to generate transgenic and knockout mice have been studied extensively. In many instances, the background strain used to create the genetic modification is inappropriate for phenotypic analysis of the mutation. In such cases it is useful to develop a congenic strain of the transgenic mouse line in which the mutation is introduced into a more suitable genetic background. In this review, the approaches to generate congenic strains of transgenic and knockout mice will be discussed. In particular, marker-assisted selection protocols (MASP) will be discussed in detail to generate congenic strains in an accelerated fashion ("speed congenics").