Increasingly, the mouse is becoming the standard model for mammalian physiology and disease. It can be genetically analyzed and manipulated with relative ease. Moreover, the endogenous genetic variation that exists among inbred mouse strains can be exploited to identify genetic control of complex physiologic processes involved in diabetes and the metabolic syndrome, among other conditions relevant to human disease. Recent advances in genetics and gene expression technology have greatly increased the knowledge to be derived from this approach when applied to traditional genetic studies.