In the last two decades the field of infrared spectroscopy has seen enormous advances in both instrumentation and the development of bioinformatic methods for spectral analysis, allowing the examination of a large variety of healthy and diseased samples, including biological fluids, isolated cells, whole tissues, and tissue sections. The non-destructive nature of the technique, together with the ability to directly probe biochemical changes without the addition of stains or contrast agents, enables a range of complementary analyses. This review focuses on the application of Fourier transform infrared (FTIR) microspectroscopy to analyse central nervous system tissues, with the aim of understanding the biochemical and structural changes associated with neurodegenerative diseases such as Alzheimer s disease, Parkinson s disease, transmissible spongiform encephalopathies, multiple sclerosis, as well as brain tumours. Modern biospectroscopic methods that combine FTIR microspectroscopy with bioinformatic analysis constitute a powerful new methodology that can discriminate pathology from normal healthy tissue in a rapid, unbiased fashion, with high sensitivity and specificity. Notably, the ability to detect protein secondary structural changes associated with Alzheimer s plaques, neurons in Parkinson s disease, and in some spectra from meningioma, as well as in the animal models of Alzheimer s disease, transmissible spongiform encephalopathies, and multiple sclerosis, illustrates the power of this technology. The capacity to offer insight into the biochemical and structural changes underpinning aetio-pathogenesis of diseases in tissues provides both a platform to investigate early pathologies occurring in a variety of experimentally induced and naturally occurring central nervous system diseases, and the potential to evaluate new therapeutic approaches.