Sulfur Mustard (HD) is a widely used chemical warfare agent, easily accessible to terrorists and thus threatening to both Army personnel and civilians. HD exposure causes blisters and skin burns, affects eyes, lungs, gastrointestinal systems, depresses bone marrow, takes several months to heal, and can lead to secondary infections and death. Nitrogen Mustard (H2N), an analogue of HD, is widely used as an anticancer agent and is associated with side effects. No effective therapy is currently available to treat HD problems. HD and other mustards are potent alkylating agents with electrophilic properties. Previous work has implicated depletion of glutathione (GSH) and generation of reactive oxygen substances (ROS) in mustard mediated toxicity. This article reviews all published works related to ROS generation and GSH depletion in studies related to HD and H2N toxicity and compares the treatments available for such conditions. The review includes in vitro cell culture models as well as in vivo animal models; receiving various concentrations of HD or H2N; and measurements of various parameters such as antioxidant enzymes, DNA and protein oxidation products, tissue damage and cell death. The results indicate that various sulfhydryl compounds, antioxidants and compounds that will increase production of endogenous scavengers show various degrees of protection against HD and H2N toxicity. However, some of these compounds are effective only if they are given before or immediately after exposure to mustards, which is of some concern for successful clinical applications.