Abstract Ratio measures, such as the ventricle-brain ratio (VBR) based on computed tomography or magnetic resonance imaging, are widely used in psychiatric research in studies of brain function and morphology. While imaging techniques have advanced considerably, the form of the index of a structure's size has remained the same—a proportion based on an estimate of the structure's size divided by a like estimate of the whole brain size. We demonstrate that ratio and similar indices can suffer greatly in reliability when compared with simple volume measures. This loss of reliability is related to the relation of a structure's size and whole brain size. We review various methods for measuring the size of structures and discuss their strengths and limitations in terms of reliability and validity. In many instances, other methods of “correcting” for brain size (e.g., regression or covariance) may yield measurements that are more appropriate than ratios.