Type 1 diabetes is the most common autoimmune disorder in childhood, characterized by the development of autoimmunity through unknown environmental insults in genetically susceptible individuals. There are now over 50 regions of the genome that harbor type 1 diabetes susceptibility genes, with much of the genetic risk now well-defined in youth of Northern European ancestry. The impact of these genetic variants on initiation and progression of the autoimmune process (islet autoimmunity) is now being understood; however, studies are only now being conducted to understand the function of the variants associated with type 1 diabetes risk. The characteristics of genetic risk of type 1 diabetes across the age spectrum suggests extensive complexity in biological and environmental mechanisms. We propose that both genetic and environmental factors attributed to type 1 and type 2 diabetes may contribute to beta-cell death through multiple mechanisms, leading to the clinical outcome of type 1 diabetes.