Tandem mass spectrometry (MS/MS) is increasingly applied to synthetic polymers to characterize chain‐end or in‐chain substituents, distinguish isobaric and isomeric species, and determine macromolecular connectivities and architectures. For confident structural assignments, the fragmentation mechanisms of polymer ions must be understood, as they provide guidelines on how to deduce the desired information from the fragments observed in MS/MS spectra. This article reviews the fragmentation pathways of synthetic polymer ions that have been energized to decompose via collisionally activated dissociation (CAD), the most widely used activation method in polymer analysis. The compounds discussed encompass polystyrenes, poly(2‐vinyl pyridine), polyacrylates, poly(vinyl acetate), aliphatic polyester copolymers, polyethers, and poly(dimethylsiloxane). For a number of these polymers, several substitution patterns and architectures are considered, and questions regarding the ionization agent and internal energy of the dissociating precursor ions are also addressed. Competing and consecutive dissociations are evaluated in terms of the structural insight they provide about the macromolecular structure. The fragmentation pathways of the diverse array of polymer ions examined fall into three categories, viz. (1) charge‐directed fragmentations, (2) charge‐remote rearrangements, and (3) charge‐remote fragmentations via radical intermediates. Charge‐remote processes predominate. Depending on the ionizing agent and the functional groups in the polymer, the incipient fragments arising by pathways (1)–(3) may form ion–molecule complexes that survive long enough to permit inter‐fragment hydrogen atom, proton, or hydride transfers. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 30:523–559, 2011