Interferon-alpha (IFN alpha) is the main therapeutic agent in patients infected with the hepatitis C virus (HCV). It is rather safe, but is known to induce the production of autoantibodies and can lead to the occurrence of autoimmune disease. This minireview focuses on the induction of autoimmune thyroid disease (AITD) in HCV-infected patients treated with IFN alpha. Females carry a higher risk to develop AITD upon IFN alpha treatment, with a relative risk of 4.4 (95% confidence interval 3.2-5.9). The presence of thyroid peroxidase antibodies before therapy has a relative risk for AITD of 3.9 (95% confidence interval 1.9-8.1). IFN alpha-associated AITD can consist of autoimmune primary hypothyroidism, Graves' hyperthyroidism, and destructive thyroiditis, with hypothyroidism being the most common side effect. The clear association between AITD and IFN alpha use suggests that high endogenous IFN alpha levels may also be associated with naturally occurring AITD. High endogenous IFN alpha levels are seen in patients infected with certain viruses. It is concluded that IFN alpha is one of the environmental factors capable of triggering the onset of AITD in genetically susceptible individuals.