The laboratory mouse, with its genetic similarity to humans and rich set of tools for manipulating its genome, has emerged as one of the key models for experimental investigation of the genotype/phenotype relationships in mammals. Recent innovations have made MRI an increasingly popular tool for examining the phenotype of genetically altered mice. Advances in field strengths, mouse handling, image analysis and statistics have contributed greatly in this regard. In this chapter, we illustrate the methods necessary to achieve high-throughput phenotyping of genetically altered mice using multiple-mouse MRI combined with advanced image analysis techniques and statistics.