Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) are two novel microsurgical techniques that can improve prosthetic control and prevent and treat chronic limb pain following amputation. Both techniques use nerve transfer to reroute the neural input from a transected nerve to new muscle targets, thereby preventing neuroma formation and creating a new functional pathway between peripheral nerves and the brain. These techniques were originally developed to improve myoelectronic bioprosthetic control, but both TMR and RPNI have expanded in their indications to the prevention and treatment of symptomatic neuromas, thus improving quality of life and decreasing the narcotic burden in this vulnerable population. This review describes the principles of TMR and RPNI, their indications, the perioperative technique, and the postoperative management of patients undergoing these procedures.