Oxidation can damage all biological macromolecules, and the survival of a cell therefore depends on its ability to control the level of oxidants. Microbes possess an astonishing variety of antioxidant defences, ranging from small, oxidant-scavenging molecules to self-regulating, homeostatic gene networks. Most often these antioxidant defences are activated by exposure to specific classes of oxidants. Interestingly, the isolation of pleiotropic mutations that impair or exacerbate the expression of subsets of oxidant-responsive genes led to the identification of global regulators. In a few, well-characterized cases, these regulators can transduce oxidative damage into gene regulation. Recently, the application of genomic tools to study the antioxidant responses of E. coli has both confirmed previous observations and provided evidence for a wealth of putative new anti-oxidant functions. Here, we review the remarkable diversity of antioxidant defence mechanisms, with emphasis on signal transduction by global regulator proteins and the corresponding genetic networks that protect the microbial cell against oxidative stress.