Osteoarthritis (OA) is a degenerative disease of cartilage and bones, which results in severely compromised quality of life in the aged population. However, currently, no ideal treatment strategies have been developed to prevent OA progression. Cell therapies, such as chondrocyte and MSC transplantation, have been extensively tested and evaluated in clinical trials. Yet, to day, the clinical efficacy of articular injection of stem cells in OA has not been convincingly demonstrated. Recent studies have indicated that exosomes, one type of Extracellular Vesicles (EVs) play an important regulatory role in the pathogenesis of OA, suggesting the prospective therapeutic application of exosomes in OA treatment. In this review, we systematically summarized the paracrine effects of exosomes derived from MSCs and chondrocytes on cartilage regeneration, the use of exosomes as a delivery vehicle for OA treatment, the effectiveness of such treatments in OA animal models, and the future perspective of exosome-mediated drug delivery as a cell- free therapy of OA.