Chemical exchange phenomena in NMR spectra reveal protein motions on microsecond to millisecond time scales that are associated with biological functions, including catalysis, ligand binding, allosteric conformational changes and protein folding. This review surveys solution NMR methods for identifying chemical exchange in proteins by measuring transverse relaxation rate constants for backbone 15N spins. The relaxation-compensated-IzSz and in-phase Hahn echo methods are suitable for small- to medium-sized proteins. The transverse relaxation optimized spectroscopy method is suitable for large, deuterated proteins. Differential multiple quantum relaxation is also a signature of chemical exchange and provides unique information about exchange processes. The various methods are illustrated by application to basic pancreatic trypsin inhibitor and triosephosphate isomerase. Copyright © 2003 John Wiley & Sons, Ltd.