It has become evident that multiple sclerosis (MS) has significant neurodegenerative components. An increasing number of reports show neuronal and axonal damage in MS patients and experimental allergic encephalomyelitis (EAE) in an animal model of MS. The mechanisms behind this neurodegeneration are unknown, but evidence suggests immune-mediated damage. In this review we analyse the findings of immune-mediated injury in MS and focus on axonal and neuronal injury. The potential neuroprotective role of some currently available MS drug treatments is also discussed.