There is evidence of a neurodegenerative process running in parallel with or as a consequence of the inflammatory phenomenon in multiple sclerosis (MS). MR imaging has been central in the generation of such knowledge and has played a pivotal role in investigating the neurodegenerative process. However, there is insufficient evidence supporting MR imaging-measured brain atrophy as a biomarker of the neurodegenerative component of MS in the daily care of patients with MS. This article discusses the prognostic value of brain volume measurements and their potential role in monitoring treatment response in patients with MS.