The genetic makeup that individuals inherit from their ancestors is responsible for variation in responses to food and susceptibility to chronic diseases such as Type 2 diabetes mellitus (T2DM). Common variations in gene sequences, such as single nucleotide polymorphisms, produce differences in complex traits such as height or weight potential, food metabolism, food-gene interactions, and disease susceptibilities. Nutritional genomics, or nutrigenomics, is the study of how foods affect the expression of genetic information in an individual and how an individual's genetic makeup affects the metabolism and response to nutrients and other bioactive components in food. Since both diet and genes alter one's health and susceptibility to disease, identifying genes that are regulated by diet and that cause or contribute to chronic diseases could result in the development of diagnostic tools, individualized intervention, and eventually strategies for maintaining health. Translating this research through clinical studies promises contributions to the development of personalized medicine that includes nutritional as well as drug interventions. Reviewed here are the key nutrigenomic concepts that help explain aspects of the development and complexity of T2DM.