This review discusses the potential of gas-phase H/D-exchange (HDX) reactions for supramolecular chemistry. The exchange of labile H against D atoms can help unravel structural details of supramolecules—in particular when combined with other gas-phase experiments, e.g. ion-mobility MS. The presence of different, non-interconverting structures in an ion population can lead to bimodal exchange distributions. Since hydrogen bonding has an effect on the exchange rates, the number and positions of hydrogen bonds can often be determined. Zwitterionic and charge-solvated structures of amino acids and peptides can be distinguished. Beyond structure, dynamic features such as the mobility of building blocks within complexes can be investigated.