In Autoimmune disease a combination of infection, genetic and environmental factors causes an autoimmune response to the thyroid gland (characterized by lymphocytic infiltrations), thyroid stimulating hormone receptor (TSHR) and different thyroid antigens. Graves' and Hashimoto disease are autoimmune disorders with genetic predisposition. CD40 that stimulates the proliferation and differentiation of lymphocytes is an essential immunomodulatory component for follicular cells in the thyroid and the cell that present the antigen. CD40, PTPN22 and thyroid-specific genes are immunomodulating genes for the TSH receptor and thyroglobulin. CD40 used to be associated with Graves's disease as positional candidate on the basis of Graves' disease linkage study connecting with 20q11 genome chromosomal region. The PTPN22 gene gives rise to a substantial risk of specific autoimmune phenotypes and frequent disease mechanisms. Infections have been implicated in the pathogenesis of AITD including Coxsackie virus, Yersinia enterocolitica, Borrelia burgdorferi, Helicobacter pylori and retroviruses (HTLV-1, HFV, HIV and SV40). Infectious hepatitis C agents are the strongest proof supporting an affiliation with AITD. The essential environmental triggers of AITD are iodine, drugs, infection, smoking and perhaps stress. Autoimmune disease provide important facts on genetic mechanisms that influence the prognosis and treatment of the disease and by recent molecular techniques through gene expression study by quantitative Real Time-PCR and microarray, we can identify novel genes which are responsible for Graves' and Hashimoto disease.