Treatment options for anterior cruciate ligament (ACL) injuries have greatly developed over the past decades. Although reconstruction surgery is a concrete reality, stimulation of ACL healing through biological techniques could represent a revolutionary conservative approach. The use of biologic products, such as platelet-rich plasma (PRP) or mesenchymal stem cells (MSCs), to treat partial ruptures or to enhance ligamentization after reconstruction, could thoroughly improve clinical outcomes. The aim of the present paper is to systematically review the available literature on this topic, to (i) describe the current state of the art in available biologic techniques;​ (ii) clarify the outcomes of their application;​ (iii) identify areas needing further investigation and possible future development. A systematic review of the literature on the use of biologically active agents (PRP and MSCs) to enhance outcomes of ACL surgery was performed:​ 31 studies were included. Based on the ACL injury pattern, 6 papers investigated biologic agents in ACL partial tears whereas 25 papers in ACL reconstruction. Sixteen of twenty-five studies dealing with ACL reconstruction were randomized controlled trials, whereas only case series are available for partial ACL tears. Current evidence is still lacking sound data to support the use of biological agents:​ no clinical superiority has been described when using PRP in ACL reconstruction. Concerning ACL healing in partial tears, the application of PRP has led to encouraging outcomes, but these findings should be confirmed by appropriately designed RCTs.