AbstractChondroitin sulfate (CS) is a ubiquitous component of the cell surface and extracellular matrix of animal tissues. CS chains are covalently bound to a core protein to form a proteoglycan, which is involved in various biological events including cell proliferation, migration, and invasion. Their functions are executed by regulating the activity of bioactive proteins, such as growth factors, morphogens, and cytokines. This review article focuses on the catabolism of CS. This catabolism predominantly occurs in lysosomes to control the activity of CS-proteoglycans. CS chains are fragmented by endo-type glycosidase(s), and the resulting oligosaccharides are then cleaved into monosaccharide moieties from the nonreducing end by exoglycosidases and sulfatases. However, the endo-type glycosidase responsible for the systemic catabolism of CS has not yet been identified. Based on recent advances in studies on hyaluronidases, which were previously considered to be hyaluronan-degrading enzymes, it appears that they recognize CS as their original substrate rather than hyaluronan and acquired hyaluronan-hydrolyzing activity at a relatively late stage of evolution.