Mass spectrometry can be used to obtain information about all levels of protein structure. To gain access to the conformation information found in the tertiary and quaternary structure, various labeling methods have been developed. These methods convert structural information into mass differences that can be observed with high-resolution protein/ peptide mass spectrometry. Three methods are reviewed here: hydrogen/deuterium exchange, covalent modification (also called chemical modification) and hydroxyl radical footprinting. The general implementation of these methods is described and comparisons are made between the methods.