The growing burden of diabetes in the United States is leading public health entities to reconsider the focus of their efforts to prevent and control the disease. In particular, they are striving to include primary prevention in their agendas. Many program reports and projects, specifically the chronic disease directors project, recommend effective ways to prevent diabetes. Science supports the need for primary prevention of diabetes, but the most effective ways to implement the chronic disease directors project's recommendations remain unclear. The purpose of this commentary is to review the programmatic challenges faced by a federal diabetes public health entity, the Division of Diabetes Translation. These include limited funding, little coordination of primary prevention efforts among disease-oriented programs, limited research on effective interventions, and the large population at risk for developing diabetes. We discuss these challenges with reference to the primary prevention of diabetes, but they have broader implications for the different public health entities (federal, state, and nongovernmental organizations) with a vested interest in diabetes because they attempt to implement similar primary prevention recommendations for other diseases.