The failure of cartilage healing is a major impediment to recovery from joint disease or trauma. Growth factors play a central role in cell function and have been proposed as potential therapeutic agents to promote cartilage repair. Decades of investigation have identified many growth factors that promote the formation of cartilage in vitro and in vivo. However, very few of these have progressed to human trials. A growth factor that robustly augments articular cartilage healing remains elusive. This is not surprising. Articular cartilage repair involves multiple cellular processes and it is unlikely that any single agent will be able to optimally regulate all of them. It is more likely that multiple regulatory molecules may be required to optimize the maintenance and restoration of articular cartilage. If this is the case, then interactions among growth factors may be expected to play a key role in determining their therapeutic value. This review explores the hypothesis that growth factor interactions could help optimize articular cartilage healing.