A great deal has been learned about the effectors and mechanisms of Type 1 diabetes from preclinical models and studies of samples from patients at risk and with the disease. However, despite this progress, translation of this understanding into new therapies that will have impact on patients has not been realized. The goal of this meeting is to review our understanding of the mechanisms that are involved in the disease with consideration of the ways in which this understanding has resulted in clinical translation and how it has failed. Our goal is to integrate the most up to date understanding of mechanisms of autoimmune diabetes with studies in patients in order to identify ways in which developments in preclinical studies can provide insight into the past experiences in clinical studies and improve the design of future studies. The meeting will explore the following areas in detail: 1) What are the genetic determinants, immunopathology, and triggers of the disease? 2) What are the immune effectors that lead to beta cell destruction – how do they form and what are their functional characteristics? 3) How are immune effectors controlled in healthy individuals and how does this control fail in T1DM? 4) What has been the experience in restoring immune tolerance in humans – how can this be improved in the future?