In the last few years considerable progress has been made with regard to the unravelling of the processes responsible for the destruction of pancreatic P-cells in the islets of Langerhans, leading to type 1 (insulindependent) diabetes mellitus. Important B-cell autoantigens have been identified, P-cell antigen specific T-cell reactivity has been described in humans, and several non-MHC linked susceptibility loci have been mapped in the NOD mouse. Attention to genetic predisposition to type 1 diabetes in humans has moved from HLA-DR to HLA-DQ, and in particular combinations of-DQ alleles of both a and B, and interest is slowly moving to non-HLA loci. The result is, that although our knowledge of the molecular basis of the disease has increased, the complexity of the genetic association and molecular processes has increased simultaneously. In this review, the latest developments in our understanding of the pathogenesis of type 1 diabetes and their implications for immunotherapy and prevention of the disease are summarized.