The extracellular matrix (ECM) is a complex network of proteins and glycosaminoglycans which surrounds cells and serves a critical role in directing cell fate and functions, as well as imparting the necessary mechanical behaviour to the tissue. To achieve successful cartilage regeneration, stem cells and/or progenitor cells have to be able to undergo an orderly spatiotemporal differentiation process, along with specific changes in the ECM expression and deposition, to form a cartilage tissue with the defined hierarchical matrix organization. In the last decade, significant advances have been made in our understanding of the role of the ECM during chondrogenesis and in cartilage homeostasis following differentiation, with some unexpected findings. This review will survey the major ECM components and their interactions with relevant stem cell populations for the regeneration of cartilage. Future therapies will likely benefit from a better understanding and a more precise control of stem cell-ECM interactions implicated in the regenerative response.