Prokaryotic cells employ redox-sensing transcription factors to detect elevated levels of reactive oxygen species and regulate expression of antioxidant genes. In Escherichia coli, two such transcription factors, OxyR and SoxR, have been well characterized. The OxyR protein contains a thiol-disulfide redox switch to sense hydrogen peroxide. The SoxR protein uses a 2Fe-2S cluster to sense superoxide generated by redox-cycling agents, as well as to sense nitric oxide. Both proteins are turned on and off with very fast kinetics (approximate minutes), allowing rapid cellular responses to oxidative stress. The mechanisms by which these and other prokaryotic proteins sense redox signals have provided useful paradigms for understanding redox signal transduction in eukaryotic cells.