I  1976, the noted human geneticist James Neel titled a book chapter “Diabetes Mellitus: A Geneticist’s Nightmare.”1 Over the past 30 years, however, the phenotypic and genetic heterogeneity of diabetes has been painstakingly teased apart to reveal a family of disorders that are all characterized by the disruption of glucose homeostasis but that have fundamentally different causes. Recently, the availability of detailed information on the structure and variation of the human genome and of new high-throughput techniques for exploiting these data has geneticists dreaming of unraveling the genetic complexity that underlies these disorders. This review focuses on type 1 diabetes mellitus and includes an update on recent progress in understanding genetic factors that contribute to the disease and how this information may contribute to new approaches for prediction and therapeutic intervention.