Glycosaminoglycans (GAGs) govern important functional characteristics of the extracellular matrix (ECM) in living tissues. Incorporation of GAGs into biomaterials opens up new routes for the presentation of signaling molecules, providing control over development, homeostasis, inflammation, and tumor formation and progression. Recent approaches to GAG-based materials are reviewed, highlighting the formation of modular, tunable biohybrid hydrogels by covalent and non-covalent conjugation schemes, including both theory-driven design concepts and advanced processing technologies. Examples of the application of the resulting materials in biomedical studies are provided. For perspective, solid-phase and chemoenzymatic oligosaccharide synthesis methods for GAG-derived motifs, rational and high-throughput design strategies for GAG-based materials, and the utilization of the factor-scavenging characteristics of GAGs are highlighted.