The last decade has seen the development of methods that use conventional magnetic resonance imaging (MRI) to provide sensitive and reproducible assessments of brain volumes. This has increased the interest in brain atrophy measurement as a reliable indicator of disease progression in many neurological disorders, including multiple sclerosis (MS). After a brief introduction in which we discuss the most commonly used methods for assessing brain atrophy, we will review the most relevant MS studies that have used MRI-based quantitative measures of brain atrophy, the clinical importance of these results, and the potential for future application of these measures to understand MS pathology and progression. Despite the number of issues that still need to be solved, the measurement of brain atrophy by MRI is sufficiently precise and accurate. It represents one of most promising in vivo measures of neuroaxonal degeneration in MS, and it should be used extensively in the future to assess and monitor pathological evolution and treatment efficacy in this disease.