The control of signal transduction involves post-translational modification of proteins at key amino acids. Cysteine residues are important in the control of 'redox' cell-signaling pathways, as thiol chemistry offers the possibility of modification by structurally diverse species, including those derived from oxidized lipids, peroxides or nitric oxide. An important and provocative study of the modification of thiols in the transcription factor OxyR recently extended this hypothesis. The findings offer the enticing possibility that the cell can distinguish between different degrees of oxidant and nitrosative exposure by modification at a single site on a signaling molecule.