Genome-wide association studies (GWAS) have facilitated a substantial and rapid rise in the number of confirmed genetic susceptibility variants for type 2 diabetes (T2D). Approximately 40 variants have been identified so far, many of which were discovered through GWAS. This success has led to widespread hope that the findings will translate into improved clinical care for the increasing numbers of patients with diabetes. Potential areas or clinical translation include risk prediction and subsequent disease prevention, pharmacogenetics, and the development of novel therapeutics. However, the genetic loci so far identified account for only a small fraction (approximately 10%) of the overall heritable risk for T2D. Uncovering the missing heritability is essential to the progress of T2D genetic studies and to the translation of genetic information into clinical practice.