Renewed interest in axonal injury in multiple sclerosis has significantly shifted the focus of research into this disease toward neurodegeneration. During the past year magnetic resonance and morphologic studies have continued to confirm and extend the concept that axonal transection begins at disease onset, and that cumulative axonal loss provides the pathologic substrate for the progressive disability that most long-term MS patients experience. Although inflammation and chronic demyelination are probable causes of axonal transection, little is known about the molecular mechanisms that are involved. The view that MS can also be considered an inflammatory neurodegenerative disease has important clinical implications for therapeutic approaches, monitoring of patients, and future treatment strategies.