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The heterogeneity and fragility of free glycans and the carbohydrate modifications to proteins and lipids present challenges for their analysis by mass spectrometry, but new instrumentation, accessories, and protocols can successfully address these challenges. Novel sample preparations, new ionization and scanning modes, and Electron-Based Dissociation (ExD) options offer opportunities to preserve labile modifications to biopolymers and provide both glycosidic and cross-ring cleavage information on glycans, on a time scale that is compatible with online nanoflow liquid chromatography and capillary electrophoresis, alone or in combination with ion mobility separations. Examples poised to meet expanding clinical and industry needs will include emergent methods that are already in use for medical studies, or are ready to move from our own or other research laboratories to the clinical laboratory.