Historically, glycomics has lagged behind other omics fields, owing to analytical challenges. However, recent technological advances are rapidly transforming the field, enabling a growing number of large-scale studies to harness the wealth of information encoded by glycans. In this Review, we provide an overview of the current state of large-scale glycomics and its role in understanding the functional importance of glycans. We discuss the main challenges in high-throughput glycoanalytical methods and highlight recent progress, with a particular emphasis on standardization and reproducibility. Special attention is given to the necessity of large, well-designed and ideally longitudinal and multicohort studies that use rigorous statistical approaches to uncover robust biological associations. Finally, we conclude with selected applications and perspectives, emphasizing the potential of large-scale glycomics to drive biomarker discovery and enhance the understanding of glycan-mediated biology.