Osteoarthritis (OA) is a progressive disease of the joints characterized by degradation of articular cartilage. Although disease initiation may be multi‐factorial, the cartilage destruction appears to be a result of uncontrolled proteolytic extracellular matrix destruction. A major component of the cartilage extracellular matrix is aggrecan, a proteoglycan that imparts compressive resistance to the tissue. Aggrecanase‐mediated aggrecan degradation is a significant event in early stage OA. The relative contribution of individual ADAMTS‐4 and ADAMTS‐5 proteinases to cartilage destruction during OA has not been resolved completely. This review reveals that both ADAMTS‐4/ADAMTS‐5 are responsible for aggrecan degradation in a human model of OA, and is expected to list down the rational strategies which are being focussed for therapeutic intervention in OA. J. Cell. Biochem. 112: 3507–3514, 2011. © 2011 Wiley Periodicals, Inc.