Simplified schematic demonstrating 2 routes of muscle atrophy: disuse or anterior cruciate ligament (ACL) injury. Inactivity or disuse can lead to muscle atrophy; however, mechanically engaging the muscle through exercise can lead to the reestablishment of healthy muscle tissue (left cycle of image). Conversely, muscle atrophy that occurs after ACL injury persists despite extensive strengthening exercises (right cycle of image). Resistance to traditional strengthening mechanisms is likely due, in part, to the various alterations in the morphological, phenotypic, and signaling pathways that are present after ACL injury and foster an environment where atrophy is more difficult to overcome. Unique to ACL injury, neurological disruptions uncouple the nervous system with muscle tissue, contributing to more complex manifestation of muscle loss, including fiber type transition, reduced satellite cells, and fatty tissue deposition, none of which are restored through traditional exercise.