Recent genome-wide association studies have been able to identify multiple new gene loci affecting type 1 diabetes susceptibility, but the impact of these new defined loci seems to decrease in parallel with their number. The HLA gene region remains the main nominator of genetic susceptibility, although the identity of important genes and especially the mechanisms of their action are still largely unclear. Products of HLA and most other known risk genes are involved in regulation of the immune system in accordance with the autoimmune nature of the disease. The multitude of genes involved in the pathogenesis implies complex pathways where multiple steps in each may be essential in turning the balance of immune response to beta-cell destructing autoimmunity.