Until recently, atrophy of the brain and spinal chord was thought to occur late in the course of multiple sclerosis (MS) or as a result of rare, fulminant disease. Now atrophy is known to occur early and likely indicates destructive and irreversible pathologic change that may be subclinical. Central nervous system atrophy from MS now can be measured accurately over short time intervals. Atrophy may become an important prognostic indicator in MS and is being evaluated as a treatment outcome measure in population studies, and possibly in the future, in individuals.