The etiology of osteoarthritis (OA) is complex, with genetic, developmental, biochemical, and biomechanical factors contributing to the disease process. Chondrocytes in articular cartilage must express appropriate genes to achieve tissue homeostasis, and this is altered in OA given the role of microRNAs in mediating the translation of target mRNAs into proteins, the identification of differentially expressed microRNAs in OA tissue and the crucial contribution that microRNAs play in the progression of OA, microRNAs may have important diagnostic and therapeutic potential, and provide a novel means of treating OA.