The ancestors of Escherichia coli and Salmonella ultimately evolved to thrive in air-saturated liquids, in which oxygen levels reach 210 μM at 37°C. However, in 1976 Brown and colleagues reported that some sensitivity persists: growth defects still become apparent when hyperoxia is imposed on cultures of E. coli . This residual vulnerability was important in that it raised the prospect that normal levels of oxygen might also injure bacteria, albeit at reduced rates that are not overtly toxic. The intent of this article is both to describe the threat that molecular oxygen poses for bacteria and to detail what we currently understand about the strategies by which E. coli and Salmonella defend themselves against it. E. coli mutants that lack either superoxide dismutases or catalases and peroxidases exhibit a variety of growth defects. These phenotypes constitute the best evidence that aerobic cells continually generate intracellular superoxide and hydrogen peroxide at potentially lethal doses. Superoxide has reduction potentials that allow it to serve in vitro as either a weak univalent reductant or a stronger univalent oxidant. The addition of micromolar hydrogen peroxide to lab media will immediately block the growth of most cells, and protracted exposure will result in the loss of viability. The need for inducible antioxidant systems seems especially obvious for enteric bacteria, which move quickly from the anaerobic gut to fully aerobic surface waters or even to ROS-perfused phagolysosomes. E. coli and Salmonella have provided two paradigmatic models of oxidative-stress responses: the SoxRS and OxyR systems.