In this article, we have summarized current facts, models and views of the autoimmunity that leads to destruction of insulin-producing beta-cells and consequent Type 1 (insulin-dependent) diabetes mellitus. The presence of strong susceptibility and resistance gene loci distinguishes this condition from other autoimmune disorders, but environmental disease factors must conspire to produce disease. The mapping of most of the genetic risk (or disease resistance) to specific alleles in the major histocompatibility locus (MHC class II) has direct functional implications for our understanding of autoimmunity in diabetes and directly implies that presentation of a likely narrow set of peptides is critical to the development of diabetic autoimmunity. While many core scientific questions remain to be answered, current insight into the disease process is beginning to have direct clinical impact with concerted efforts towards disease prevention or intervention by immunological means. In this process, identification of the critical antigenic epitopes recognized by diabetes-associated T cells has achieved highest priority.