Hypobromous acid (HOBr) and hypothiocyanous acid (HOSCN) are produced by a number of human peroxidase enzymes, including myeloperoxidase (MPO), eosinophil peroxidase (EPO), and lactoperoxidase (LPO), via the reaction of hydrogen peroxide with bromide (Br) and thiocyanate (SCN) ions, respectively [1–6]. HOBr and HOSCN are chemical oxidants that react with biological molecules and cells with quite different potency and selectivity [1,7]. In each case, these oxidants are critical in immune defense, as each has powerful antibacterial, antiviral, and antifungal properties (e.g., [8–13]). However, in some cases, the overproduction of these oxidants during chronic inflammation has been implicated in the development of disease [12,13]. For example, HOBr is believed to contribute to tissue damage in the lungs of patients with asthma, shown by the detection of elevated amounts of the biomarker 3-bromo-Tyr [12,14]. In contrast to HOBr, which is generally regarded as a damaging oxidant, the role of HOSCN in disease is unclear. Thus, some studies provide evidence to support cellular damage on exposure to this oxidant, which may exacerbate disease (reviewed [7,13]), while others support a potentially protective role of elevated SCN in inflammatory disease (reviewed [15,16]). 328This chapter will review the formation and reactivity of HOBr and HOSCN in biological systems, and discuss the implications of these reactions in both immune defense and disease.