Selenoprotein P (SeP) is a selenium-rich extracellular glycoprotein and is the major selenoprotein in plasma. SeP is presumed to be composed of two domains: one possesses redox-enzyme activity containing one selenocysteine residue in the N-terminal region, and the other functions as a selenium supplier containing nine selenocysteine residues in the C-terminal region. These domains are connected by a bridge containing two histidine-rich regions. Although the relationship between structure and function is not clear, SeP is reported to function as a peroxynitrite scavenger, or cell survival factor in the primary culture of neurons. Thus, SeP is a multifunctional protein. Increasing evidence indicates that SeP plays a significant role in vivo in the maintenance of selenium levels in the brain and testis. In the present review, we describe the structural properties and molecular function of SeP and discuss its significant role in cellular homeostasis, particularly in relation to selenium levels and the antioxidative system.