Osteoarthritis (OA) is characterized by articular cartilage degeneration in the joints and results in pain, swelling, stiffness, muscle atrophy, and attendant functional disability. The progression of OA cannot be prevented by drugs. Current treatments for OA focus on symptomatic relief of pain. Recently, platelet-rich plasma (PRP) injection has attracted much attention for modulating articular cartilage and synovial membrane in OA. Despite the increasing interest in PRP for the treatment of OA, the precise mechanisms underlying the actions of PRP on OA remain unclear. We have reviewed the known actions of PRP in the joint. The in vitro and in vivo evidence is reviewed concerning the potential of the modulation of PRP on normal articular cartilage and OA progression. PRP modulates the repair and regeneration of damaged articular cartilage in the joints and delays the degeneration of cartilage by stimulation of mesenchymal stem cell migration, proliferation, and differentiation into articular chondrocytes. In addition to the symptomatic relief, PRP is a biological response modifier of inflammatory nuclear factor-κB signaling pathway and PRP reduces the pain by decreasing inflammation and angiogenesis of the synovial membrane where pain receptors are localized. PRP has the therapeutic potential not only to promote tissue regeneration, but also to contribute to articular cartilage lubrication by decreasing the friction coefficient and minimizing wear. Although further refinements and improvements are needed in standardized PRP preparations, PRP may modulate regeneration of articular cartilage and retards the progression of OA by stimulating cell migration, proliferation, differentiation of progenitor/stem cells, joint homeostasis, and joint lubrication.