Type 1 diabetes (T1D) and the autoimmune thyroid diseases (AITD) are the most common autoimmune endocrine diseases. Both are organ-specific T-cell mediated diseases. Abundant epidemiological data support a strong genetic basis for both T1D and AITD. Furthermore, both diseases commonly occur in the same individuals and in the same families. Indeed, studies suggest that the etiology of T1D and AITD may involve common genetic factors. Two immune regulatory genes, HLA and CTLA-4 contribute to the susceptibility to both diseases. Additionally, two tissue-specific genes, the insulin VNTR in T1D and Thyroglobulin in AITD play a major role in their pathogenesis. Therefore, it is likely that both immune regulatory and target tissue genes contribute to these and other autoimmune diseases.