The prevalence of type 2 diabetes mellitus has increased worldwide over the past decades. The economic and social cost associated with diabetes mellitus and its complications have also increased enormously. Since current methods of treating diabetes is inadequate, the most effective way to reduce the burden associated with type 2 diabetes would be to prevent diabetes itself. Current strategies to prevent type 2 diabetes mellitus are based on efforts to reduce insulin resistance and to preserve or increase pancreatic beta cell function in high risk individuals. Now there is substantial evidence that life style intervention or pharmacologic agents can reduce the development of diabetes in individuals with impaired glucose tolerance. However, it remains to be determined whether the result would be similar in other risk groups for type 2 diabetes. Although development of type 2 diabetes mellitus is influenced by a complex interaction between genetic and environmental factors, current prevention strategies do not reflect contribution of genetic factors. Over the past decade, many investigators tried to find diabetogenic genes by traditional gene discovery methods. It appears that multiple genes with weak effect are involved in the development of type 2 diabetes mellitus which makes searching diabetogenic genes more complicated. In addition to the completion of human genome project, new genetic tools to identify genetic variations and analyze gene to gene or gene to environmental interaction will facilitate the discovery of susceptibility genes for type 2 diabetes mellitus in near future. Once we could identify susceptibility genes and gene to environmental interaction of type 2 diabetes mellitus, we can clarify the role of both environmental and genetic factors in the development of type 2 diabetes mellitus. Moreover, we can identify people who can get more benefit from prevention and also can provide better and personalized preventive measure based on genetic information.