Cortical plasticity is a finely regulated process that allows the central nervous system (CNS) to change in response to internal and external stimuli. While these modifications occur throughout normal brain development, interestingly, they are also elicited after peripheral nerve injury and surgery. This article provides an overview of the principle mechanisms of synaptic, neuronal, cortical and subcortical neuroplasticity, with special attention to cortical and subcortical modifications-as suggested by modern neuroimaging techniques-after peripheral nerve surgery. The main nerve transfer techniques for the superior extremities and their effect on cortical plasticity are also described.