The thyroid gland produces high concentrations of hydrogen peroxide (H₂O₂) which is used for the biosynthesis of the thyroid hormones, triiodothyronine and thyroxine. The most important step in thyroid hormone synthesis is oxidation and organification of iodide, which itself is a very potent oxidant. To oxidize iodide, thyrocytes generate high intracellular concentrations of H₂O₂ using the NADPH-dependent dual oxidase enzymes (DUOX) and remove used H₂O₂ by various well-characterized antioxidant systems, such as those involving glutathione peroxidases and peroxiredoxins. Although thyrocytes have very intricate and efficient systems to regulate H₂O₂ generation and removal, leakage of H₂O₂ may be inevitable because of the high intracellular concentrations of H₂O₂ in thyrocytes. Leakage of the highly reactive oxidant H₂O₂ is likely to cause the damage to various intracellular proteins and DNA that has been demonstrated to be a causative factor in the induction of various diseases, such as thyroid cancer, chronic thyroiditis and hyperthyroidism. Therefore, ongoing investigation of the systems regulating H₂O₂ production and elimination in thyrocytesis essential for understanding the regulation and process of thyroid hormone synthesis and also for elucidating pathogenetic mechanisms underlying various autoimmune thyroid diseases and the initiation and promotion of thyroid cancers.