Cysteine residues on proteins react with cellular oxidants such as hydrogen peroxide, superoxide, and peroxynitrite. One product of these reactions, cysteine sulfenic acid (Fig. ), is linked to a variety of redox regulation mechanisms and signalling pathways, and may serve as a biomarker for oxidative stress. To understand the cellular and physiological roles of cysteine sulfenic acid, it is important to be able to detect its formation on proteins. 1 Such analyses are challenging because cysteine sulfenic acids are sometimes short-lived. Additionally, selective detection of the sulfenic acid oxidation state must occur in the presence of thiols, disulfides, sulfinic acids and other derivatives of cysteine.