There is considerable evidence that placental oxidative stress plays a significant role in the etiology of preeclampsia. Prophylactic use of exogenous anti-oxidants such as Vitamins E and C have proven to be ineffective and potentially dangerous. The current study addresses the role of endogenous anti-oxidant systems in preeclampsia. In particular, data on the selenodependent enzymes glutathione peroxidase and thioredoxin reductase will be presented and the role of selenium in preeclampsia will be considered. The aim of these studies was to determine the levels of endogenous antioxidants, selenium, and biological oxidation in normal and preeclamptic placental tissues. Cellular studies using transformed trophoblast cells showed that selenium supplementation could enhance antioxidant enzymes expression and protect from oxidative stress. Furthermore, selenium depletion in animal models decreased the endogenous expression of anti oxidant enzymes generating placental oxidative stress and produced a preeclamptic like syndrome in pregnant rats suggesting a link between placental oxidative stress, endogenous antioxidant disequilibria and the pathogenesis of preeclampsia that may be linked to insufficient dietary selenium. The selenium of status of preeclamptic mothers was also considered and lower levels of selenium were observed when compared to normal controls. Selenium supplementation improves endogenous anti-oxidant expression in trophoblast cells and might provide an effective method of protecting the placenta from oxidative stress during preeclampsia. Clinical studies are now underway to investigate the benefits of low dose selenium supplementation on the development and progression of preeclampsia.