Triphenylphosphonium (TPP) ylides, or Wittig reagents, are widely used in organic chemistry for the synthesis of alkenes. Shi et al. now extend their utility to bioorthogonal chemistry for the labeling of sulfenic acid, a post-translationally oxidized form of cysteine. After validating this reaction with a dipeptide model, the authors synthesized several alkyne-functionalized Wittig reagents (WYne probes) that formed stable adducts with peptides and proteins in aqueous solution, were selective for sulfenic acid over other redox cysteine modifications, and facilitated subsequent conjugation via click chemistry. These WYne probes can also enter live cells with minimal cytotoxicity, enabling biological applications such as chemoproteomics to profile cellular S-sulfenylome dynamics and quantification of the fraction of proteins with S-sulfenylation at particular sites. Since TPP moieties are commonly used as mitochondria-localization tags, WYne probes could also be utilized for in situ TPP tagging of target proteins for their delivery to mitochondria. The development of these Wittig reagent–based probes adds a versatile reaction to the bioorthogonal toolbox for monitoring and controlling cysteine modifications.