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Phantom pain refers to pain in a body part that has been amputated or deafferented. It has often been viewed as a type of mental disorder or has been assumed to stem from pathological alterations in the region of the amputation stump. In the past decade, evidence has accumulated that phantom pain might be a phenomenon of the CNS that is related to plastic changes at several levels of the neuraxis and especially the cortex. Here, we discuss the evidence for putative pathophysiological mechanisms with an emphasis on central, and in particular cortical, changes. We cite both animal and human studies and derive suggestions for innovative interventions aimed at alleviating phantom pain.