Like many great inventions, serendipity played a significant role in the discovery of electron capture dissociation (ECD). In the late 1990s, McLafferty et al. unexpectedly observed c- and z-type fragment ions when irradiating peptide and protein cations with 193 nm UV light (see Figure 2.1).^1,2  It was eventually found that the formation of these fragments involved recombination of the analyte cations with photoelectrons generated by 193 nm photons impinging on metal surfaces in their Fourier transform ion cyclotron resonance (FTICR) instrument. Thermodynamically, of the three types of bond in the backbone of a protein (N–Cα, Cα–C(O), C(O)–N) the weakest is the amide (C(O)–N) and this is the preferred cleavage site in ‘slow-heating’ fragmentation techniques such as collision-induced dissociation (CID) or infrared multiphoton dissociation (IRMPD).³  In those methods, the internal energy is increased with each collision or photon absorption and then redistributed relatively evenly across the analyte's internal degrees of freedom, resulting in fragmentation of the weakest bonds, which happens over a relatively long timescale (microseconds to seconds). To account for the fragmentation pattern they observed, McLafferty et al. postulated that cleavage of the N–Cα bond occurred almost immediately after electron capture, i.e., too fast to allow for statistical redistribution of energy across vibrational modes (which normally occurs on a picosecond timescale).²  This is known as non-ergodic behaviour, and the (non-)ergodicity of ECD remains contentious to this day. As we will see, the mechanism proposed by McLafferty et al. in 1998 was further refined to what is now known as the ‘Cornell mechanism’, after the university where the McLafferty laboratory was based. The main alternative is provided by the ‘Utah–Washington mechanism’, after the universities where its two primary developers, Simons and Tureček, respectively, performed this work. We will also discuss other proposed mechanisms for ECD, and consider a closely related reaction, electron transfer dissociation (ETD).⁴  While ECD and ETD are relatively selective for cleavage of the N–Cα bond, we will also discuss side reactions, most notably loss of amino acid residue side chains. Finally, we will look at how these techniques are implemented in practice, and see how this has evolved from the production of photoelectrons to the development of compact, flexible ECD cells that can be installed on a range of mass spectrometers.