Glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides that interact with a variety of positively harged growth factors. In order to form tissue-engineered constructs, GAGs can be easily chemically modified for assembly into carriers of cells and biomolecules. Such modifications generally include functionalization to form three-dimensional scaffolds for a wide range of applications. However, chemical modifications can have effects on protein binding, as well as affect degradation processes, which, in turn, influence molecular release characteristics. Therefore, this chapter provides a review of GAG structure and protein-binding properties as well mechanisms of GAG degradation, followed by specific examples of how different modified GAG species have been employed in tissue-engineered constructs. Overall, GAG-based polymers are a versatile biomaterial platform offering novel means to engineer cellular and molecular delivery with a high degree of control in order to better treat a range of degenerate or injured tissues.