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Mass spectrometers, instruments that use electric and/or magnetic fields to measure a gas-phase ion's mass-to-charge ratio (m/z), are used in a wide variety of applications—with the field having a reputation for providing good sensitivity and high-informing power. Protein analysis (proteomics) is a relatively recent affair for the field and was enabled in the late 1980s with the advent of biomolecule ionization methods such as electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI). Today, the area of protein analysis garners considerable attention from many in the mass spectrometry (MS) field; given the myriad of possible protein forms and their broad dynamic range (abundance) in the cell, the analytical challenge is paramount. Here we discuss a developing technology—ion/ion chemical reactions—that promises to transform how we think about and conduct protein sequence analysis via MS.