The hitherto identified hallmarks of the autoimmune aspects in Type 1 diabetes are reviewed. Their implication in the disclosure of the pre-clinical phase of the disease is put forward. The possible delineation of this pre-diabetic phase can lead to an early immunotherapeutic approach. The effect of immunomodulation by agents such as azathioprine, cyclosporin A and nicotinamide in newly diagnosed diabetes and the use of some of these drugs in clinical trials on pre-diabetic individuals are discussed.