Proteoglycans and glycosaminoglycans are the main components of the extracellular matrix of the nucleus pulposus. Intervertebral disc degeneration due to aging and excessive mechanical loads results in adverse quantitative and structural changes to the macromolecules. Metalloproteinases induced by inflammatory mediators play a key role in degrading proteoglycans. Progressive matrix breakdown decreases water content in the disc. Dehydration compromises disc cells function and impairs resistance to compression. Biochemical changes may result in disc prolapse. Modifying the metabolism of proteoglycans and glycosaminoglycans might be an effective therapeutic strategy.