Publisher Summary The compound ebselen is considered capable of contributing to the antioxidant defense in tissues. Many of the biological properties of ebselen were explainable on the basis of its property as an enzyme mimic, carrying out the function of the selenoenzyme, GSH peroxidase (GPx), and of phospholipid hydroperoxide GSH peroxidase (PHGPx). It is obvious that the biological functions of ebselen might extend to other reactions in addition to the reduction of hydroperoxides. Biologically occurring selenoproteins deactivates peroxynitrite. A further aspect resides in the high reactivity of ebselen with thiol groups, leading to the inactivation or inhibition of enzymes. This chapter discusses synthesis of ebselen, molecular activities of ebselen, activity in biological model systems, metabolism, clinical assessment, and other selenoorganic compounds. An assay systems for the detection of GPx-like activity have been described—coupled enzymatic assay, assay of GSH removal, and assay of hydroperoxide removal. There is scavenging of peroxynitrite—peroxynitrite (ONOO-IONOOH), a strong oxidizing species, is generated in inflammatory processes from the superoxide anion radicaland nitric oxide. The formation of peroxynitrite by various cell types, such as macrophages and endothelial cells has been detected. The peroxynitrite-induced luminol chemiluminescence emitted from Kupffer cells was inhibited in the presence of low concentrations of ebselen, and ebselen rapidly reacts with peroxynitrite in a bimolecular fashion, yielding the selenoxide of the parent molecule, ebselenSe-oxide[2-phenyl-l,2-benzisoselenazol-3(2H)-one I-oxide], as the sole selenium-containing product at 1:1 stoichiometry. Radical scavenging and singlet oxygen quenching have been mentioned, along with ebselen's reactivity with protein thiols. GPx-like activity of ebselen is involved in the protection of intact cells against lipid peroxidation. Ebselen protects against different types of oxidative attack by acting in its capacity as a GPx mimic, and, in particular, as a PHGPx mimic. It is capable of preventing copper-dependent LDL oxidation in the presence of GSH.