Glycoproteomics reveals site-specific O- and N-glycosylation that may influence protein properties including binding, activity, and half-life. The increasingly mature toolbox with glycomic and glycoproteomic strategies is applied for the development of biopharmaceuticals and the discovery and clinical evaluation of glycobiomarkers in various disease fields. Notwithstanding the contributions of glycoscience in identifying new drug targets, the current report is focused on the biomarker modality that is of interest for diagnostic and monitoring purposes. To this end, it is noted that the identification of biomarkers has received more attention than the corresponding quantification. Most analytical methods are very efficient in detecting large numbers of analytes, but developments to accurately quantify these have so far been limited. In this perspective, a parallel is made with earlier proposed tiers for protein quantification using mass spectrometry. Moreover, the foreseen reporting of multimarker readouts is discussed to describe an individual’s health or disease state and their role in clinical decision-making. The potential of longitudinal sampling and monitoring of glycomic features for diagnosis and treatment monitoring is emphasized. Finally, different strategies that address the quantification of a multimarker panel are discussed.