Background: Oxidative stress is caused by an imbalance between the production of Reactive Oxygen Species (ROS) and the ability to detoxify them with the help of antioxidants. The premature infant is especially susceptible to ROSinduced damage because of inadequate antioxidant stores at birth, as well as impaired upregulation in response to oxidant stress. Thus, the premature infant is at increased risk for the development of ROSinduced diseases of the newborn, such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and periventricular leukomalacia. Purpose of Review:This review will examine the unique susceptibility of premature infants to oxidative stress, the role of reactive oxygen species (ROS) in the pathogenesis of common disorders of the preterm infant, and potential for therapeutic interventions using enzymatic and/or nonenzymatic antioxidants. Methodology: An extensive search was made on internet as well as Neonatology textbooks were referred for this review. Summary: Potential therapies for ROSinduced disease include both enzymatic and nonenzymatic antioxidant preparations. More research is required to determine the beneficial effects of supplemental antioxidant therapy.