Oxidative stress plays a key role in numerous disease processes including chronic kidney disease (CKD). In general, oxygen metabolism leads to the formation of reactive oxygen species (ROS) dangerous to cells. Although enzymes and low-molecular-weight antioxidants protect against ROS, chronic imbalances of formation and elimination can eventually overwhelm endogenous defenses leading to deleterious consequences. In CKD, glutathione peroxidases (GSH-Px) play an important role in ROS metabolism. Plasma GSH-Px is synthesized in the kidney and requires selenium (Se) as a cofactor. Interestingly, Se and plasma GSH-Px are both significantly reduced in CKD, especially for those patients on hemodialysis. Supplementation of Se in these patients results in modest increases of GSH-Px, presumably from residual renal tissue. Kidney transplantation rapidly restores plasma GSH-Px. In this chapter, the relevance of these findings to CKD is explored with emphasis on renal disease processes and impact on attendant disorders including cancer and cardiovascular disease.