The elucidation of several genetic etiologies of both monogenic and polygenic type 2 diabetes (T2D) has revealed several key regulators of glucose homeostasis and insulin secretion in humans. Genome-wide association studies (GWAS) have been instrumental in most of these recent discoveries. The T2D susceptibility genes identified so far are mainly involved in pancreatic β-cell maturation or function. However, common DNA variants in those genes only explain ∼10% of T2D heritability. The resequencing of whole exomes and whole genomes with next-generation technologies should identify additional genetic changes that contribute to the monogenic forms of diabetes and possibly provide novel clues to the genetic architecture of common adult T2D.