Autoimmune thyroid diseases (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex diseases that arise due to interplay between environmental and genetic factors. In the past decade, several AITD susceptibility genes have been identified and characterized, including both immune-regulatory genes and thyroid-specific genes. Some of these susceptibility genes are specific to either GD or HT, while others confer susceptibility to thyroid autoimmunity in general. Recent studies began dissecting the mechanisms by which these new genes predispose to thyroid autoimmunity, and the emerging mechanisms focus on abnormalities of the immunological synapse. In this chapter, we will summarize the recent data on the genes predisposing to AITD and the emerging mechanisms by which they confer susceptibility to disease.