Type 2 Diabetes results from a complex physiologic process that includes the pancreatic beta cells, peripheral glucose uptake in muscle, the secretion of multiple cytokines and hormone-like molecules from adipocytes, hepatic glucose production, and likely the central nervous system. Consistent with the complex web of physiologic defects, the emerging picture of the genetics will involve a large number of risk susceptibility genes, each individually with relatively small effect (odds ratios below 1.2 in most cases). The challenge for the future will include cataloging and confirming the genetic risk factors, and understanding how these risk factors interact with each other and with the known environmental and lifestyle risk factors that increase the propensity to type 2 diabetes.