Mass spectrometry is a powerful technique for molecular characterization. Although the mass of intact ions is often revealing, most experiments employ further activation to generate fragments that provide additional information. In essence the fragments reveal sub-structural elements that can be stitched back together, much like pieces of a puzzle. For example, the identity of a peptide can be inferred by fragmentation that dissects out the whole or partial sequence of amino acids. Within this paradigm, it is often viewed as desirable to generate as many fragments as possible, thereby increasing the amount of data and potential for extracting useful information. Significant effort has therefore been directed with this intent. For example, collision-induced dissociation (CID)¹  has been augmented with higher-energy collisional dissociation (HCD)^2,3  that produces more fragments. Similarly, electron-capture and electron-transfer dissociation (ECD, ETD)^4,5  have been improved by various means of introducing supplemental activation.^6–8  The standard ‘full annihilation’ approach to mass spectrometry has proven very useful, but it suffers from drawbacks as well. For example, it can generate highly complicated spectra that are difficult to interpret, and it is challenging to predict or control the outcome for any given experiment. Exceptions have also been noted during the course of these experiments, where dissociation is highly directed and yields a small number of fragments. These exceptions have drawn significant attention because they often reveal information about underlying mechanisms that lead to fragmentation. They have also inspired efforts to develop means for intentionally controlling where and how molecules fragment by bond-selective dissociation.