Infectious agents are considered as etiologic factors for the onset of Graves' disease, while psychosocial stress and smoking may amplify the pathogenic cascade. Furthermore, smoking increases the risk of developing Graves' ophthalmopathy. Occasional evidence indicates that the autoimmune process may primarily be induced by foreign antigens, leading to the synthesis of antibodies which, in part, cross-react with thyrocytic TSH receptors. Once initiated, autoimmunity appears sustained within the thyroid by the cooperation of immunomodulated thyrocytes and antigen-presenting dendritic cells, which may, moreover, cause humoral responses against further thyrocytic antigens. Owing to a local increase in cytokine and integrin expression, lymphocytes and monocytes are attracted to the organ. The synthesis of autoantibodies is mainly propagated by T-helper-2 cells, while, at the same time, T-suppressor cells appear to be functionally deficient. Proof for this hypothetical scenario may allow for novel immunotherapeutic onsets in the near future.