Hashimoto's thyroiditis (HT) is the most prevalent thyroid autoimmune disorder, characterized by the presence of specific thyroid autoantibodies (TAb). The development of autoimmunity, including TAb production and clinical presentation of HT, is determined by a complex interplay of genetic susceptibility and several endogenous and environmental factors, which are discussed in this article. During the progression of the disease, TAb production precedes clinical manifestations, although the correlation between TAb concentrations and thyroid function is weak. We do not treat euthyroid HT patients despite elevated TAb; while in hypothyroidism, replacement therapy with l-thyroxine is required. Until now, an effective approach to prevent TAb production and the development of clinical disease has not yet been established. However, further identification of risk factors and their interaction may help in the prevention of thyroid autoimmunity.