Excess reactive oxygen species (ROS) generation and oxidative stress in vascular tissue is associated with many diseases. Glutathione (GSH), one of the most abundant low molecular weight non-protein thiols, modulates physiological levels of ROS and is involved in the cell's oxidative stress response. The GSH/GSSG redox couple is commonly used in measuring oxidative stress status. The imbalance of GSH is reported in many disease states including atherosclerosis, cancer, neurodegenerative disease, and aging. The importance of GSH in modulation of intracellular ROS involves both its protective defense against the damaging effects of oxidative stress and its role in facilitating ROS cell signaling. In this paper, we review significant results obtained from mass balance and kinetic reactions based computational and mathematical models of GSH participation in oxidative stress. The focus is on the mediation of ROS and oxidative stress with respect to the antioxidant capacity of the cell. We discuss the role of GSH in the redox state of the cell, maintaining homeostasis through GSH synthesis, scavenging of free radicals, modulating hydrogen peroxide level and interacting with nitric oxide pathways.