Type 1 diabetes mellitus is preceded by autoimmunity against the insulin-producing islet beta cells. Autoantibodies against islet antigens such as insulin, glutamic acid decarboxylase, and the protein tyrosine phosphatase-like molecule IA-2 are found in most patients with type 1 diabetes and are now established markers for the clinical diagnosis and the preclinical phase of this disease. The development of islet autoantibodies and diabetes is influenced by genetic and environmental factors, and the detection and characterization of islet autoantibodies in euglycemic members of affected families identifies some individuals who have a markedly elevated risk for type 1 diabetes. This ability to accurately predict diabetes risk in non-diabetic subjects will prove very useful for targeted recruitment of participants of interventional studies aimed at preventing the progression to type 1 diabetes in subjects at risk.