Recent advances in genome wide surveys for common DNA sequence variants have contributed a great deal to our understanding of the pathophysiology of diabetes, but currently identified genetic loci are insufficient to explain individual or ethnic differences in risk of type 1 or type 2 diabetes. Nonetheless, interactions between our current diet and lifestyle and both our genetic background and that of our harbored gut microbiota, are likely to underpin the growth of diabetes observed today. This chapter summarizes the following: (1) progress in defining the genetic contribution to type 1 and type 2 diabetes, (2) gene–environment and gene–therapy interactions, and (3) limitations of the current data and future potential studies.