The extracellular matrix (ECM) is a complex composite biomaterial with critical structural and functional roles to play in connective tissues. The cells embedded within the ECM provide the biosynthetic machinery for the synthesis and secretion of the complex array of interactive molecules that are required for its assembly. The major components of ECMs are glycoproteins, collagens, proteoglycans, and elastin. ECMs are heterogeneous both between connective tissues and within a single tissue type during development/maturation or with ECM remodeling events associated with pathologic processes. Some connective tissues are highly cellular and contain relatively little ECM (e.g., muscle, kidney, liver) whereas others contain an abundant ECM and relatively few cells (e.g., cartilage, tendon). Some tissues contain mineralized matrices (e.g., bone, dentine) whereas the ECM of others have gel-like consistencies (e.g., vitreous humour, synovial fluid, Wharton's jelly), reflecting their relative contributions to weight bearing, internal organ cushioning, or lubrication of joint surfaces. For the purposes of this chapter, cartilage was selected as a representative tissue because of its relatively simple structure, containing ∼5% cells but approximately 90% ECM. The chondrocytes in hyaline cartilage, however, have well-defined pericellular, territorial, and inter-territorial matrices and characteristic cellular arrangements (chondrons) in the superficial, intermediate, and deep zones of this tissue. It is therefore possible to identify different functional compartments in the cartilage ECM and to categorize the proteins within them, which offers heuristic advantages.