Hydroxide-catalyzed exchange of the amide hydrogens on the protein backbone provides a highly sensitive monitor of electrostatic interactions at the aqueous interface. Much of the practical utility of these ionizations, relative to the more widely studied sidechain titrations, stems from the brief (∼10 ps) lifetime of the peptide anion intermediate which strongly limits the contribution of conformational reorganization to dielectric shielding such that electronic polarizability dominates the dielectric response of the protein. The increased sensitivity to the local electrostatic environment is manifested in the billion-fold range in exchange rates for amides that are exposed to solvent in high resolution X-ray structures. Yet to date, the exchange rates for 56 solvent exposed amides from four wellcharacterized proteins are predictable by standard continuum dielectric methods to within a factor of 7, comparing quite favorably to analogous sidechain titration analyses. Quantification of electronic interactions from short range local backbone geometry to long range formal charge effects facilitates their use in addressing questions of more general chemical interest, including the longstanding issue of whether the peptide anion charge resides primarily on the ionizing nitrogen or is transferred to the carbonyl oxygen to form an imidate ion. More fundamentally, hydrogen exchange provides experimental demonstration of the magnitude of systematic errors in the predicted electrostatic potential that can arise when dielectric shielding due to electronic polarizability is neglected in standard nonpolarizable force fields for which the electrostatic energies are optimized at the expense of accuracy in the electric field distribution.