Publisher Summary GSHPx-1 is a housekeeping gene functioning in the detoxification of hydrogen peroxide and various fatty acid hydroperoxides, which use glutathione as a reducing agent. This chapter presents a study in which homozygous knockout mice were apparently normal, fertile, and healthy upon observation to 20 months of age. No increase sensitivity to hyperoxia was found in the knockout mice compared to the wild type. However, the platelets from GSHPx-1–/– mice were less capable of metabolizing 12-HPETE to 12-HETE at a high concentration of arachidonic acid. The knockout mice were also more sensitive to paraquat toxicity and ischemia/reperfusion heart injury compared to wild-type mice.