Upper extremity amputation can lead to significant functional morbidity. The main goals after amputation are to minimize pain and maintain or improve functional status while optimizing the quality of life. Postamputation pain is common and can be addressed with regenerative peripheral nerve interface surgery or targeted muscle reinnervation surgery. Both modalities are effective in treating residual limb pain and phantom limb pain, as well as improving prosthetic use. Differences in surgical technique between the 2 approaches need to be weighed when deciding what strategy may be most appropriate for the patient.