Type 1 diabetes mellitus (T1DM) affects 1 in 300 people and the incidence of the disease is rising worldwide. T1DM is caused by chronic autoimmune destruction of the insulin-producing beta-cells. The exact etiology and primary auto-antigen are not yet known. The autoimmune, chronic, and progressive nature of the disease raises the possibility of intervention, preferably by slowing down or stopping the destruction of the beta-cells as early as the prediabetic stage. Since the 1980s, several attempts have been made to maintain beta-cell function using immunosuppressive agents, immune modulation such as plasmapheresis, cytokine therapy, or antibody treatment. These agents were not diabetes specific; the occasionally observed beneficial effect did not compensate for the often very severe side effects. According to the latest assumption, the administration of diabetes-specific auto-antigens can elicit tolerance, which can prevent the destruction of the beta-cells, hopefully without serious side effects. The authors summarize current understanding of the immunology of T1DM, review the trials on prevention, and discuss their vaccination study.