Genetic susceptibility to type 1 diabetes (DM1) and type 2 diabetes (DM2) is determined by complex genetic factors. Until recently, only a few loci were known, but this is changing rapidly as a result of the development of high-density genotyping arrays that have permitted genome-wide association studies. Several recent reports of such studies have increased our understanding of the genetics of diabetes by increasing the number of known loci to more than ten for each type of diabetes. The known DM1 genes are mainly involved in central immunotolerance in the thymus and in immune injury in the pancreas. The known DM2 genes are mainly involved in pancreatic β-cell function and peripheral insulin sensitivity. Compared with DM1 and DM2, monogenic diabetes is much rarer, and in most cases these genetics have been elucidated with classical genetic approaches. The novel physiologic insights derived from these new discoveries are discussed.