The restoration and rehabilitation of human movement are of great interest to the field of neural interfaces, i.e. devices that utilize neural activity to control computers, limb prosthesis or powered exoskeletons. Since motor deficits are commonly associated with spinal cord injury, brain injury, limb loss, and neurodegenerative diseases, there is a need to investigate new potential therapies to restore or rehabilitate movement in such clinical populations. While the feasibility of neural interfaces for upper and lower limbs has been demonstrated in studies in human and nonhuman primates, their use in investigating brain plasticity and neural mechanisms as result of clinical intervention has not been investigated. In this chapter, we address this gap and present examples of how neural interfaces can be deployed to study changes in cortical dynamics during motor learning that can inform about neural mechanisms.