Neuroanatomical structures may be profoundly or subtly affected by the interplay of genetic and environmental factors, age, and disease. Such effects are particularly true in healthy ageing individuals and in those who have neurodegenerative diseases. The ability to use imaging to identify structural brain changes associated with different neurodegenerative disease states would be useful for diagnosis and treatment. However, early in the progression of such diseases, neuroanatomical changes may be too mild, diffuse, or topologically complex to be detected by simple visual inspection or manually traced measurements of regions of interest. Computerised methods are being developed that can capture the extraordinary morphological variability of the human brain. These methods use mathematical models sensitive to subtle changes in the size, position, shape, and tissue characteristics of brain structures affected by neurodegenerative diseases. Neuroanatomical features can be compared within and between groups of individuals, taking into account age, sex, genetic background, and disease state, to assess the structural basis of normality and disease. In this review, we describe the strengths and limitations of algorithms of existing computer-assisted tools at the most advanced stage of development, together with available and foreseeable evidence of their usefulness at the clinical and research level.