In mammals and some bacteria, small molecular weight (∼10kDa) selenoprotein W (SelW) includes a single selenocysteine (Sec) residue in the Cys-X-X-Sec redox motif of the N-terminal region. It is expressed in a broad range of organisms, from mammals to bacteria. It is ubiquitously distributed in many tissues, and especially highly expressed in the skeletal muscle, heart and brain. Although many bacterial and frog SelW-like proteins contain Cys instead of Sec, it is highly conserved in many species of primates, domestic animals, rodents, amphibians, fish and bacteria. SelW is down- or up-regulated in response to oxidative stress, which suggests a redox function. SelW has Cys-X-X-Sec or Cys-X-X-Cys, both of which function as catalytic sites of redox proteins, such as thioredoxin, and allows reversible binding of glutathione to the Cys-37 residue of its protein. Moreover, since cells that overexpress SelW are resistant to exogenous oxidative stress, it is suggested that SelW may participate in an antioxidant function. However, the exact physiological function and enzymatic activity of SelW are largely unknown. This chapter will review what is currently known about SelW.