In addition to sequencing of denatured proteins and peptides, electron-based dissociation methods (ExD), such as electron capture dissociation (ECD) and electron transfer dissociation (ETD), can be used for elucidating the three-dimensional structures of native proteins and complexes. The history and current application of these methods in electrospray ionization mass spectrometry (ESI-MS) are described in this chapter. Other techniques that can be integrated with ExD-MS are briefly described, including chemical crosslinking, hydrogen–deuterium exchange, and ion mobility.