Most patients with amputation (up to 80%) suffer from phantom limb pain postsurgery. These are often multimorbid patients who also have multiple risk factors for the development of chronic pain from a pain medicine perspective. Surgical removal of the body part and sectioning of peripheral nerves result in a lack of afferent feedback, followed by neuroplastic changes in the sensorimotor cortex. The experience of severe pain, peripheral, spinal, and cortical sensitization mechanisms, and changes in the body scheme contribute to chronic phantom limb pain. Psychosocial factors may also affect the course and the severity of the pain. Modern amputation medicine is an interdisciplinary responsibility. This review aims to provide an interdisciplinary overview of recent evidence-based and clinical knowledge. The scientific evidence for best practice is weak and contrasted by various clinical reports describing the polypragmatic use of drugs and interventional techniques. Approaches to restore the body scheme and integration of sensorimotor input are of importance. Modern techniques, including apps and virtual reality, offer an exciting supplement to already established approaches based on mirror therapy. Targeted prosthesis care helps to obtain or restore limb function and at the same time plays an important role reshaping the body scheme. Consequent prevention and treatment of severe postoperative pain and early integration of pharmacological and nonpharmacological interventions are required to reduce severe phantom limb pain. To obtain or restore body function, foresighted surgical planning and technique as well as an appropriate interdisciplinary management is needed.