The assessment of brain volume changes on serial magnetic resonance imaging (MRI) scans can provide an objective measure of progressive atrophy reflecting the neurodegenerative aspects of multiple sclerosis (MS) pathology. The present article reviews the results of studies assessing the effect of glatiramer acetate (GA) treatment in preventing MS-related, MRI-measurable brain volume decrease. Whilst data from the extended, open-label follow-up of the US trial seem to indicate that long-term treatment with GA might prevent the loss of brain parenchyma in relapsing-remitting MS patients, longitudinal data from the European/Canadian MRI trial suggest that, over a short-term period of treatment, GA does not have a clear-cut impact on the decrease of brain volume. The effect of GA on MS-related brain atrophy might, therefore, be delayed and dissociated in time from those exerted on other clinical and MRI measures of disease activity. However, the modest magnitude of this effect makes it difficult to evaluate its impact on the actual disease progression. Further studies of adequate duration are now required to address this issue, as well as to confirm the sustained efficacy of GA treatment over long periods of follow-up.