The understanding that the human brain is capable of structural and functional change throughout life has significant implications for the future of physical therapy. Cortical plasticity impacts on many areas of physical therapy including clinical practice, research and education. Although the principles of plasticity underpin developments in neurological physical therapy, relevance to musculoskeletal physical therapy is still emerging. How will key areas of musculoskeletal physical therapy change as our understanding of plasticity advances? If cortical plasticity can be harnessed, new plasticity-based therapies, that enhance performance in healthy individuals and improve pain and function in patient populations, have the potential to become the cornerstone of musculoskeletal physical therapy. In addition, common physical therapy techniques, such as electrical stimulation, require reconsideration of their clinical efficacy and application in light of new discoveries in neuroscience. The aim of this appraisal is to provide an update on brain plasticity for physical therapists in relation to clinical practice, research and education.