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The persistently high incidence of knee ligament injuries has spurred a growing interest in the biology of ligament healing. Similarly, the recognition that healed ligament tissue is structurally inferior to the intact ligament has focused efforts on potential biologic interventions aimed at improving the quality of healed tissue. A host of in vitro and in vivo studies have recently begun to elucidate the role of several growth factors in regulating ligament healing in structures such as the medial collateral ligament. Evidence that growth factors may promote cell proliferation and protein synthesis have prompted an interest in gene transfer technology as a means to enhance long-term growth factor expression in injured ligaments. This manuscript will review current knowledge of the effects of growth factors on ligament healing in light of potential biologic interventions.