In acute multiple sclerosis (MS) lesions, axonal pathology and the number of transected axons correlate with the number of immune cells and therefore with inflammatory activity. In addition to the commonly described white matter locations, demyelination also occurs in the gray matter of MS patients. The concept of MS as an inflammatory demyelinating and neurodegenerative disease provides a framework to help explain disease progression and development of permanent neurological disability in MS patients. Prevention of persistent neurological disability is the main goal when treating neurological diseases. In contrast to most neurodegenerative diseases, patients with MS can be identified early before the occurrence of extensive neurodegeneration by the presentation of symptoms mediated by inflammatory demyelination. Therefore, neuroprotective therapeutics may have a greater probability of clinical efficacy in MS patients since treatment can be initiated before extensive axonal loss. Regardless of the cause of MS, axons and neurons are important therapeutic targets.