Growth factors are obvious tools to enhance cartilage repair. Understanding of reactivities in normal and arthritic cartilage and potential side effects on other compartments in the joint will help to identify possibilities and limitations. Growth factor responses have been evaluated in normal and diseased murine knees. The main cartilage anabolic factor, insulinlike growth factor-1, shows great safety, but has little contribution in diseased cartilage because of insulinlike growth factor nonresponsiveness of arthritic chondrocytes. Transforming growth factor-beta can overrule interleukin-1 catabolic effects and can enhance cartilage repair in arthritic tissue, unlike bone morphogenetic protein-2 that only is capable of enhancing chondrocyte proteoglycan synthesis in the absence of interleukin-1. Transforming growth factor-beta and bone morphogenetic protein-2 induce chondrophyte formation at the margins of the joint. Studies with scavenging transforming growth factor beta soluble receptor identified endogenous transforming growth factor-beta involvement in spontaneous cartilage repair and chondrophyte and subsequent osteophyte formation in arthritic conditions. Osteophyte induction may hamper intraarticular transforming growth factor-beta application in the joint and warrants targeted growth factor application to cartilage lesion sites only.