Inbred mouse strains provide genetic diversity comparable to that of the human population. Like humans, mice have a wide range of diabetes-related phenotypes. The inbred mouse strains differ in the response of their critical physiological functions, such as insulin sensitivity, insulin secretion, β-cell proliferation and survival, and fuel partitioning, to diet and obesity. Most of the critical genes underlying these differences have not been identified, although many loci have been mapped. The dramatic improvements in genomic and bioinformatics resources are accelerating the pace of gene discovery. This review describes how mouse genetics can be used to discover diabetes-related genes, summarizes how the mouse strains differ in their diabetes-related phenotypes, and describes several examples of how loci identified in the mouse may directly relate to human diabetes.