Testing of autoantibodies in individuals at risk of developing or being newly diagnosed with diabetes mellitus is currently of very limited clinical value. However, clinical studies evaluating new therapeutic options for the delay or treatment of type 1 diabetes mellitus require sensitive, specific, and reliable assays for autoimmune antibodies associated with diabetes mellitus. With immune modulatory treatment of pre-diabetes mellitus on the horizon the need of reliable assays is evident. In addition, determination of autoimmune antibodies in diabetes mellitus facilitates studies investigating the pathophysiology underlying this disease. Clinicians and researchers should be aware of the tests available, their limitations, their clinical relevance, and their indications. This review focuses on the current knowledge about antibody assays for diabetes associated autoimmunity, their clinical value, their role in diagnosing and predicting autoimmune associated diabetes mellitus, and research applications.