Publisher Summary Metal- and flavin adenine dinucleotide (FAD)-dependent sulfhydryl oxidases catalyze the oxidation of thiols to disulfides with a concomitant reduction of molecular oxygen to hydrogen peroxide. There are two evolutionarily unrelated classes of flavin-linked sulfhydryl oxidases. That secreted from Aspergillus niger contains FAD and a redox-active cystine bridge 4 and is most closely related to alkyl hydroperoxide reductase in the pyridine nucleotide oxidoreductase family. The sulfhydryl oxidase from egg white contains the same redox moieties, but is a member of a newly recognized gene family, which is broadly distributed from Caenorhabditis elegans to human fibroblasts. Sequence analysis of this sulfhydryl oxidase/Quiescin Q6 family shows an N-terminal thioredoxin domain, an intervening region, and a C-terminal ALR/ERV domain. This chapter focuses on the egg white enzyme because it is the best understood member of this burgeoning enzyme family. Its preferred substrates are protein or peptide sulfhydryl groups, not low molecular weight thiols, such as cysteine or glutathione. Quiescin Q6 is a secreted flavoprotein oxidase and may, therefore, counterbalance extracellular reductive processes.