The structure and reactivity of the cysteine methyl ester radical cation, CysOMe.+, have been examined in the gas phase using a combination of experiment and density functional theory (DFT) calculations. CysOMe.+ undergoes rapid ion–molecule reactions with dimethyl disulfide, allyl bromide, and allyl iodide, but is unreactive towards allyl chloride. These reactions proceed by radical atom or group transfer and are consistent with CysOMe.+ possessing structure 1, in which the radical site is located on the sulfur atom and the amino group is protonated. This contrasts with DFT calculations that predict a captodative structure 2, in which the radical site is positioned on the α carbon and the carbonyl group is protonated, and that is more stable than 1 by 13.0 kJ mol−1. To resolve this apparent discrepancy the gas-phase IR spectrum of CysOMe.+ was experimentally determined and compared with the theoretically predicted IR spectra of a range of isomers. An excellent match was obtained for 1. DFT calculations highlight that although 1 is thermodynamically less stable than 2, it is kinetically stable with respect to rearrangement.