Over the past ~15 years there has been great progress in our understanding of the genetics of both type 1 diabetes and type 2 diabetes. This has been driven principally by genome-wide association studies (GWAS) in increasingly larger sample sizes, where many distinct loci have now been reported for both traits. One of the loci that dominates these studies is the TCF7L2 locus for type 2 diabetes. This genetic signal has been leveraged to explore multiple aspects of disease risk, including developments in genetic risk scores, genetic commonalities with cancer, and for gaining insights into diabetes-related molecular pathways. Furthermore, the TCF7L2 locus has aided in providing insights into the genetics of both latent autoimmune diabetes in adults and various presentations of type 1 diabetes. This review outlines the knowledge gained to date and highlights how work with this locus leads the way in guiding how many other genetic loci could be similarly used to gain insights into the pathogenesis of diabetes.