Neurodegenerative disorders, such as Alzheimer’s disease (AD), are associated with characteristic patterns of neuropathological spread in the brain. Disease progression is usually accompanied by regional atrophy that can be detected noninvasively using structural magnetic resonance imaging (MRI). A wealth of data has demonstrated the value of quantitative measurements of regional atrophy in AD, suggesting that volumetric MRI (vMRI) may be a useful clinical tool. vMRI provides biological evidence of neurodegenerative disease in patients with cognitive impairment. However, several hurdles impede implementation of vMRI in clinical practice. These include a lack of standardized MRI acquisition protocols, spatial distortions in MRI data, labor-intensive vMRI methods susceptible to interoperator variability, a lack of normative ranges for volume measures, and difficulty integrating vMRI in clinical workflow. Advances in vMRI have resulted from multi-institutional studies of brain imaging, such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI), and help address these challenges. New, fully-automated measures of brain structure volumes coupled with large, multi-center studies using standardized MRI protocols now allow the development of age-adjusted normative ranges for vMRI. Such advances are critical for providing physicians a framework for assessing the pattern and degree of regional atrophy in a patient's brain and applying vMRI in clinical practice.