CONTEXT: Autoantibodies to glutamate decarboxylase, islet antigen-2, insulin, and zinc transporter-8 are characteristic of type 1 diabetes. They are detectable before clinical onset and define the subgroup of patients with latent autoimmune diabetes in adults. Autoantibody assays are increasingly available to clinicians. This article reviews the prognostic significance of autoantibodies and considers the utility of diabetes antibody testing in routine clinical practice. EVIDENCE ACQUISITION: The medical literature to May 2009 was reviewed for key articles and consensus statements covering use of islet autoantibody testing for prediction and classification of diabetes and implications for therapy. EVIDENCE SYNTHESIS: Sensitive and specific glutamate decarboxylase and islet antigen-2 antibody assays are widely available, although to insulin autoantibody assays remain variable. Islet autoantibodies appear early in life, and testing for multiple antibodies identifies unaffected individuals at very high risk of type 1 diabetes with high sensitivity. This is important for research, but currently no intervention prevents or delays diabetes, and evidence of benefit from awareness of risk is weak. In non-insulin-treated diabetes, patients with autoantibodies progress to insulin requirement more rapidly, but evidence that testing benefits the individual patient is limited. Antibody testing is useful in classifying diabetes of other types. CONCLUSIONS: Islet autoantibody testing allows prediction of type 1 diabetes and definition of the latent autoimmune diabetes in adults subgroup of non-insulin-treated patients. Although useful for research, until therapies modulating the disease process become available, the benefit to individual patients is generally questionable. With a few exceptions, diabetes antibody testing does not yet have a role in routine clinical care.