In this issue of Molecular Microbiology, Gu and Imlay show that a class of compounds known as redox-cycling agents directly activate the transcription factor SoxR of Escherichia coli and cause cellular toxicity independent of the production of the reactive oxygen species superoxide. Despite the fact that redox-cycling agents increase formation of superoxide in E. coli, the results described in this new publication revise the long-held assumption that superoxide is responsible for the activation of SoxR and for all of the major toxic effects of redox-cycling drugs. This study also suggests that the critical function of the SoxRS regulon in E. coli is in protection against redox-cycling agents and not exclusively the defence against superoxide.