Magnetic resonance imaging (MRI)-based brain volumetry is increasingly being used in the clinical setting to assess brain volume changes from structural MR images in a range of neurologic conditions. Measures of brain volumes have been shown to be valid biomarkers of the clinical state and progression by offering high reliability and robust inferences on the underlying disease-related mechanisms. This review critically examines the different scenarios of the application of MRI-based brain volumetry in neurology: 1) supporting disease diagnosis, 2) understanding mechanisms and tracking clinical progression of disease, and 3) monitoring treatment effect. These aspects will be discussed in a wide range of neurologic conditions, with particular emphasis on Alzheimer's disease and multiple sclerosis. J. Magn. Reson. Imaging 2013;37:1–14. ©2012 Wiley Periodicals, Inc.