Osteoclast-associated receptor (OSCAR) is a member of the leukocyte receptor complex (LRC)-encoded protein family, which is characterized by the presence of immunoglobulin (Ig)-like domains. OSCAR recognizes collagen and was first identified as a co-stimulatory receptor that is needed for complete osteoclast differentiation. However, it is now clear that OSCAR is also expressed by multiple immune cells that participate in many innate and adaptive immune cell activities. We also showed recently that chondrocytes express OSCAR. Our and other studies suggest that OSCAR participates in the pathogenesis of two common joint diseases, namely, rheumatoid arthritis (RA) and osteoarthritis (OA). Specifically, OSCAR promotes osteoclast formation and therefore bone erosion in RA while in OA, it triggers chondrocyte death, thereby inducing cartilage fragility. Significantly, blocking the interaction of OSCAR with its collagen ligand can markedly reduce these activities in vitro and in vivo. Thus, this novel approach may have therapeutic potential for joint diseases.