The seminal discovery in 1956 that Hashimoto thyroiditis (HT) is an autoimmune disease spelled the end of the concept of horror autotoxicus and introduced the reality of human autoimmunity. In the same year, Graves disease (GD) was discovered to be directly caused by a serum factor, subsequently identified as an autoantibody. Perhaps because of relatively effective treatment and the absence of a strong financial reason for pharmaceutical companies to develop a cure, GD and HT, the most common organ-specific diseases affecting humans, are not targeted for intensive investigation. Nevertheless, these diseases have served as invaluable models for understanding the pathogenesis of organ-specific autoimmunity in general. Whereas autoimmune thyroiditis occurs spontaneously in some susceptible animals (rodents and chickens), there is no spontaneous animal model of GD. Induced animal models of autoimmune thyroiditis have been available for many years. More recently, antibody-mediated hyperthyroidism has also been induced in rodents by a number of imaginative approaches (reviewed in ref. 1). However, in this Perspective, we will focus on human disease, which, although more difficult to study than animal models, is likely to generate information more relevant to human pathology.