It is well known that the adult brain is capable of profound plasticity. Much of our understanding of the mechanisms underlying injury-induced changes in the brain is based on animal models. The development of sophisticated noninvasive neuroimaging techniques over the past decade provides a unique opportunity to examine brain plasticity in humans. In this article, the authors examine the consequences of nerve injury and surgical repair on peripheral nerve degeneration and regeneration and review classic animal literature that laid the foundation of injury-induced plasticity research. They relate these concepts to recent findings of functional and structural changes in the human brain following peripheral nerve injury. They then present a working theoretical model that links behavioral outcomes of nerve injury with functional and structural brain plasticity and personality.