Osteoarthritis is a common, degenerative joint disease with significant socio-economic impact worldwide. There are currently no disease-modifying drugs available to treat the disease, making this an important area of pharmaceutical research. In this review, we assessed approaches being explored to directly inhibit metalloproteinase-mediated cartilage degradation and to counteract cartilage damage by promoting growth factor-driven repair. Metalloproteinase-blocking antibodies are discussed, along with recent clinical trials on FGF18 and Wnt pathway inhibitors. We also considered dendrimer-based approaches being developed to deliver and retain such therapeutics in the joint environment. These may reduce systemic side effects while improving local half-life and concentration. Development of such targeted anabolic therapies would be of great benefit in the osteoarthritis field.