The dual oxidases (DUOXes) 1 and 2 are named based on their having both a domain homologous to the NADPH-oxidase of the phagocyte NADPH-oxidase gp91( phox )/NOX2 and a domain homologous to thyroid peroxidase. The DUOX1 and DUOX2 mRNAs were originally cloned from thyroid tissue, and the corresponding proteins were recognized as intricate components of the thyroid hormone synthesis process, providing hydrogen peroxide essential for the organification of iodide. The function of DUOX2 in thyroid hormonogenesis has been firmly established by linking the congenital hypothyroid phenotype "total iodide organification defect" to biallelic inactivating DUOX2 mutations. Based on the expression of both DUOXes in combination with a peroxidase in a range of different tissues and functional studies; the concept evolves that DUOX is important not only for thyroid hormonogenesis but also as an integral part of the host defense system of mucosal surfaces, participates in the control of epithelial infection, augments surface B-cell receptor signaling in lymphocytes, and is involved in generating a respiratory burst at fertilization.