BackgroundDysfunction in efferent pathways after knee pathology is tied to long-term impairments in quadriceps and hamstrings muscle performance, daily function, and health-related quality of life. Understanding the underlying etiology is crucial for effective treatment and prevention of poor outcomes, such as post-traumatic osteoarthritis or joint replacement. ObjectivesTo synthesize recent evidence of efferent pathway dysfunction (i.e., motor cortex, motor units) among individuals with knee pathology. DesignCommentary. MethodWe summarize the current literature investigating the motor cortex, corticospinal tract, and motoneuron pool in individuals with three common knee pathologies: anterior cruciate ligament (ACL) injury, anterior knee pain (AKP), and knee osteoarthritis (OA). To offer a complete perspective, we draw from studies applying a range of neuroimaging and neurophysiologic techniques. ResultsAdaptations within the motor cortices, corticospinal tract, and motoneuron pool are present in those with knee pathology and underline impairments in quadriceps and hamstrings muscle function. Each pathology has evidence of altered motor system excitability and reduced volitional muscle activation and force-generating capacity, but few impairments were common across ACL injury, AKP, and OA studies. These findings underscore the central role of the motor cortex and motor unit behavior in the long-term outcomes of individuals with knee pathology. ConclusionsAdaptations in the efferent pathways underlie persistent muscle dysfunction across three common knee pathologies. This review provides an overview of these changes and summarizes key findings from neurophysiology and neuroimaging studies, offering direction for future research and clinical application in the rehabilitation of joint injuries.