Antigen presenting cells (APC) be they dendritic cells (DC) or macrophages reside in all tissues. Their role varies from presenting antigen, clearing the tissue from unwanted material, helping in the remodeling that follows injury and inflammation, to a supporting or trophic function. Their features, biology, and turnover may be unique for each organ, modulated by the particular anatomy and physiology of the tissue. These features affect the handling and presentation of antigens, either exogenous such as those from viruses or bacteria, or endogenous, autologous proteins in situations of autoimmunity. Herein, we focus on the resident APC of the islets of Langerhans and their role in autoimmune diabetes. The intra-islet APC are central cells in diabetogenesis by presenting beta cell derived antigens and by modulating the localization of T cells into the islets.