A century ago, the incidence of both Type 1 (T1D) and Type 2 (T2D) was very low. Worldwide epidemics of both T1D and T2D have placed tremendous burdens on both affected individuals and society. Disproportionate resources are spent on complications of the diseases. Although multiple etiologies have been promulgated, for T1D, causative factors and the precise mechanisms leading to the disease remain elusive. In contrast, the rising incidence of T2D in children is closely associated with the obesity explosion which is strongly linked to an increased food supply and decreased physical activity. The rising incidence of obesity has reached pandemic proportions with more than a billion people affected worldwide. Focus needs to be directed to understanding the complex interaction between genes, the environment, and the immune system culminating in T1D and tackling the obesity epidemic. This chapter will discuss the emergence of the diabetes explosion, the proposed pathogenic mechanisms, and potential interventions.