Anterior cruciate ligament (ACL) tears is a devastating injury and one of the most common knee injuries experienced by athletes in the United States. Although patients reach maximal subjective improvement by one-year following ACL reconstruction, many patients often experience moderate to severe post-operative pain. Opioids, intra-articular injections, and regional anesthesia have been previously implemented to mediate post-operative pain. However, chronic opioid usage has become an epidemic in the United States. Alternative analgesic modalities, such as nerve blocks, have been implemented in clinical practice to provide adequate pain relief and minimize opioid usage. Periarticular injections targeted towards local neurological structures performed concomitantly with nerve blocks provides superior pain relief and satisfaction than isolated nerve blocks. Therefore, it is imperative for physicians to understand local neurological anatomy around the knee joint in order to provide adequate analgesia while minimizing opioid consumption. This purpose of this investigation is to summarize (1) neurogenic origins of pain generators and mediators in sites affected by ACL reconstruction and autograft harvest sites and (2) analgesia utilized in ACL reconstruction.