Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are prevalent autoimmune diseases, affecting up to 5% of the general population. Autoimmune thyroid diseases arise due to complex interactions between environmental and genetic factors. Significant progress has been made in our understanding of the genetic and environmental triggers contributing to AITD. However, the interactions between genes and environment are yet to be defined. Among the major AITD susceptibility genes that have been identified and characterized is the HLA-DR gene locus, as well as non-MHC genes including the CTLA-4, CD40, PTPN22, thyroglobulin, and TSH receptor genes. The major environmental triggers of AITD include iodine, medications, infection, smoking, and possibly stress. Recent data on the genetic predisposition to AITD lead to novel putative mechanisms by which the genetic-environmental interactions may lead to the development of thyroid autoimmunity.