Upper extremity amputation is an uncommon but often necessary procedure. It can be required as a result of trauma, infection, or malignancy. Amputation is a life-changing procedure. Careful planning for it must not only include the level of amputation and assurance of durable soft-tissue coverage of the amputation site, but it must also consider patients’ goals and occupations, as well as social factors affecting amputees. The choice of prosthesis is an individual matter, but new technology permits lighter and more multifunctional prostheses. Targeted muscle reinnervation can be used to achieve improved myoelectric signaling and possibly decrease limb pain following amputation. Rehabilitation is crucial to achieving favorable results.