The diagnosis of type 1 diabetes versus other forms of diabetes such as type 2 diabetes is paramount to guiding proper therapy. Several islet autoantibodies have been identified that serve to diagnose immune-mediated, type 1a diabetes in clinically ambiguous cases. These autoantibodies also serve to predict type 1 diabetes in nondiabetic individuals. The most useful islet autoantibodies include islet cell cytoplasmic autoantibodies, insulin autoantibodies, glutamic acid decarboxylase autoantibodies, and insulinoma-associated-2 autoantibodies. Once type 1 diabetes can be safely and reliably prevented, large-scale islet autoantibody screening programs of the general pediatric population may be warranted. It is controversial whether islet autoantibodies influence the course of type 1 diabetes following diagnosis.