Magnetic resonance imaging (MRI) reveals that brain and spinal cord atrophy occur early in the course of multiple sclerosis (MS), far earlier than originally anticipated. This has important implications for the early treatment of patients with MS, as atrophy is thought to reflect destructive, irreversible pathology, and subclinical impairment if not overt disability. Several recent trials in MS have included atrophy as a secondary or exploratory measure of treatment efficacy. While measured cerebral volume or spinal cord area changes are small over 1 to 3 year intervals, they are sufficiently large that with current methodologies the atrophy measures should provide conclusive information as to the effectiveness of therapeutic interventions in halting progressive atrophy. Atrophy measures may also provide an important metric for the evaluation of disease in primary progressive MS, and in testing combined therapies and neuroprotective agents, where conventional MRI methodologies may be relatively weak.