Diabetes is a chronic disease defined by hyperglycemia. Varying degrees of insulin resistance and/or dysfunction of the insulin producing beta cells of the pancreas cause diabetes. The disease phenotype is heterogeneous and can be divided into different subtypes depending on the underlying genetic and pathophysiologic cause (Fig. 1). Forms of diabetes due to mutations in single genes are rare (2–5% of diabetes cases), have high penetrance, and have little influence from environmental factors. In contrast, the common forms of diabetes—type 1 diabetes (T1DM) and type 2 diabetes (T2DM)—are diseases with important genetic underpinnings, but with no clear pattern of inheritance. The disease phenotypes result from the interaction of multiple gene variants, each exerting only a modest effect, and the environment. Recent research has suggested that the number of gene variants that contribute to these disease phenotypes may be much larger than previously understood, and the precise genes that are involved have been difficult to identify [1, 2]. However, when grouped with other variants and acting either contemporaneously or over time, relatively insignificant changes wrought by individual gene variants may work additively or synergistically to cause disease. Though we report on several gene variants in this review, the critical role of environment cannot be understated. The incidence of T2DM and obesity is increasing throughout the world, a trend that appears to result from changing dietary patterns and decreased physical activity [3]. These changes are thought to create a milieu conducive to the development of T2DM in genetically susceptible individuals. Thus, genes for the common forms of diabetes are best regarded as susceptibility genes and not disease genes per se.