The best understood sensors of oxidative stress are the OxyR and SoxR proteins in E. coli. SoxR has an iron-sulfur center that acts as a sensor, whereas OxyR is regulated by formation of an intramolecular disulfide bond. Less clear is how eukaryotic cells sense oxidative stress. Delaunay et al. examined the response of yeast to H2O2 through the Yap1 protein, a transcription factor that regulates the expression of genes, such as those encoding antioxidants or components of the glutathione pathway, that allow adaptation during exposure to reactive oxygen species. They find that Yap1 itself has two cysteine residues that are required for activation of the transcriptional response. Exposure to H2O2 may cause formation of a disulfide bond between these residues, which could then explain the conformational change in Yap1 that allows masking of a nuclear export signal and thus promotes transcriptional activity of the protein. Unlike OxyR, Yap1 appears not to be sensitive to the general redox state of the cell. Indeed another oxidant, diamide, appears to influence Yap1 through a distinct mechanism. Also, inactivation of Yap1 was mediated by the thioredoxin pathway, but not the glutathione pathway. These findings support a role of Yap1 as a specific sensor of peroxide concentrations rather than a monitor of the general glutathione redox balance of the cell.