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Anterior cruciate ligament (ACL) injuries are known to have very low rates of spontaneous healing. There have been several studies since the mid-1960s concerning the approaches to accelerate spontaneous healing of ACL injuries. Recent studies have identified similarities in the healing response of ACL and other extra-articular ligaments, in terms of their cellular response and vascularity. Research has demonstrated that mechanical stress has an important influence on the biological response of tissue healing. Novel treatment approaches may exploit the role of mechanical loads on the regulation of gene expression in achieving spontaneous healing of injured ACL. This article reviews the determinants of the ACL healing response and their relationship to mechanical stress and spontaneous healing, and explores novel concepts that are emerging in the management of ACL injuries.