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Infertility is a global health problem and it is one of the most stressful conditions amongst married couples. Even though not lethal, it has been described as a radical life changing problem that carries with it significant psychological trauma. Infertility can be caused by various problems and sometimes it is not possible to establish a cause. Oxidative stress, which arises from an imbalance between reactive oxygen species (ROS) and protective antioxidants, influences the entire reproductive lifespan of men and women. ROS can modulate cellular functions, and oxidative stress can disturb the intracellular milieu, resulting in diseased cells or endanger cell survival. Under normal conditions, antioxidants act to oppose ROS production, scavenging existing free radicals and promoting the repair of ROS-induced damage to cell structures. At controlled levels, oxidative stress facilitates some physiological reproductive functions but at higher levels it is implicated in pathological processes in the reproductive tract that contribute to infertility and poor pregnancy outcomes. As high levels of reactive oxygen species and low antioxidant status have been implicated in conditions contributing to infertility, treatment based on strategies to boost the exhausted antioxidant defense of the reproductive microenvironment is intuitive. Glutathione is a natural body antioxidant, which helps preserve all other antioxidants. It is present in both the male and female gametes and its level varies widely. This study reviews the role oxidative stress plays in both male and female infertility, and the antioxidant action of glutathione on infertility.