Context: The rating of perceived effort (RPE) is a common method used in clinical practice for monitoring, loading control, and resistance training prescription during rehabilitation after rupture and anterior cruciate ligament reconstruction (ACLR). It is suggested that the RPE results from the integration of the afferent feedback and corollary discharge in the motor and somatosensory cortex, and from the activation of brain areas related to emotions, affect, memory, and pain (eg, posterior cingulate cortex, precuneus, and prefrontal cortex). Recent studies have shown that rupture and ACLR induce neural adaptations in the brain commonly associated with the RPE. Therefore, we hypothesize that RPE could be affected because of neural adaptations induced by rupture and ACLR. Study Design: Clinical review. Level of Evidence: Level 5. Results: RPE could be directly altered by changes in the activation of motor cortex, posterior cingulate cortex, and prefrontal cortex. These neural adaptations may be induced by indirect mechanisms, such as the afferent feedback deficit, pain, and fear of movement (kinesiophobia) that patients may feel after rupture and ACLR. Conclusion: Using only RPE for monitoring, loading control, and resistance training prescription in patients who had undergone ACLR could lead to under- or overdosing resistance exercise, and therefore, impair the rehabilitation process. Strength-of-Recommendation Taxonomy: 3C.