Osteoarthritis (OA) is the most common form of arthritis, resulting in substantial disability and economic burden worldwide. While its exact pathogenesis remains elusive, both in vitro and human population-based studies have merged to support the hypothesis that TGF-β/BMP-mediated signalling pathways play a role in the development of OA. Unraveling the TGF-β/BMP-mediated mechanism(s) in OA has great potential in identifying novel targets and developing new drugs for OA treatment. This review summarizes both in vitro and in vivo evidence of TGF-β/BMP-mediated signal transduction pathways in OA and discusses the future research direction in this regard.