The Personalized Diabetes Medicine Program, funded by U01 HG007775 as part of the IGNITE (Implementing Genomics in Practice) Network, is designed to implement, disseminate and evaluate outcomes of a sustainable approach to detect, genomically diagnose and provide individualized therapy to people with monogenic diabetes. Monogenic forms of diabetes account for approximately 1-2% of all cases of diabetes mellitus but have been found to only be correctly diagnosed only about 95% of the time. Differentiating between monogenic and other diabetes types is crucial to correctly target treatment, as individuals with certain types of monogenic diabetes are optimally treated with sulfonylureas or no treatment rather than insulin used for type 1 diabetes and metformin used as the first line treatment for type 2 diabetes. A simple questionnaire and routine laboratory tests are used to screen all individuals with diabetes at four practice sites (an urban academic medical center, a VA medical center, a suburban endocrinology private practice and an integrated health system) for features consistent with monogenic diabetes. Individuals likely to have monogenic diabetes are tested using a 40-55 gene NGS sequencing panel. Causal mutations and potential treatment implications are reported to the patient and provider and incorporated into the electronic health record. The project includes engagement with a payer panel to enhance our ability to collect meaningful evidence.