Multiple Sclerosis (MS) is associated with a chronic demyelinating and axonal injury to the central nervous system. Functional activation studies in MS patients have demonstrated that performance of simple motor tasks may activate non-canonical brain regions. Using virtual lesion induction by transcranial magnetic stimulation, it is possible to show that this activation is functionally relevant. Rapid-onset neuronal plasticity in patients with mild-to-moderate MS is uncompromised despite many plasticity-impeding factors. Long-term adaptive mechanisms, relying on the formation on new neuronal connections, most likely are the principal mechanism underlying compensation of brain injury in MS.