About 150 million people suffer from type 2 diabetes in the world today and it has been predicted that this number will be doubled within 15 years [1]. It is no longer a disease of the elderly, age at onset has decreased with the epidemic increase in prevalence. There are large ethnic and geographic variations in the prevalence of type 2 diabetes. In Scandinavia, where type 1 diabetes is common, type 2 diabetes accounts for about 85% of all cases with diabetes. However, the distinction between type 1 and type 2 diabetes may not be as clear as hitherto thought. In addition, the disease seems to be quite heterogeneous [2]. There is plenty of evidence that type 2 diabetes is inherited, the life time risk in offspring of one diabetic parent is about 40% and the relative risk (λs) for a sibling to a patient with type 2 diabetes is about 3. It is though unlikely that the cause of the explosion of diabetes is found in our genes. It is rather the rapid change of the environment with an affluent westernized society which triggers the epidemic in genetically predisposed individuals. What then makes up this genetic predisposition? In general, the chronic hyperglycemia characteristic of type 2 diabetes require both insulin resistance in muscle and liver and impaired insulin secretion in pancreatic β-cells. Insulin resistance by itself cannot cause diabetes. As long as the β-cell can compensate for the degree of insulin resistance, glucose tolerance remains normal. Accumulation of abdominal fat often predates the manifestation of these defects. It has therefore been suggested that the normal function of the subcutaneous adipose tissue is to serve as a buffer for excess intake of fat. When this buffer capacity is exceeded the body starts to deposit fat in places where it normally does not belong, eg muscle, liver and β-cells. According to this hypothesis a common defect could explain all defects. There is, however, no proof for this and it is likely that the genetic predisposition involves several pathways in different organs. Type 2 diabetes is considered a paradigm for a multifactorial polygenic disease where common variations in several genes interact (epistasis) to cause the disease when exposed to the affluent environment of too much food and too little exercise. In the following we will discuss potential candidates which could contribute to this genetic predisposition to type 2 diabetes.