Fourier Transform Infrared microspectroscopy (FTIRM) is as a method to measure bone quality at the microscopic level by providing information on bone composition such as mineral:matrix ratio, carbonate substitution, collagen maturity and collagen fibre bond alignment. FTIR has proven to be a useful method in detecting changes in bone quality between normal and osteoporotic bone, particularly when bone mineral density measurements and biochemical markers fail to distinguish fracture patients from nonfractured patients. This method has predominantly been used in the field of bone biology to analyse bone composition in thin sections from mice, but has more recently become applicable to larger animals through the use of reflectance FTIR which allows thicker tissue sections from rabbit and monkey to be analysed. One advantage of FTIR analysis is that it can be used in combination with fluorescent labels to account for heterogeneous tissue where bone surfaces may be undergoing formation and/or resorption. This allows for the analysis of bone composition as a function of anatomic location and bone maturity. More recently, we have applied this method to evaluating how current and ermerging therapeutics modify bone composition at different bone surfaces. While FTIRM analysis cannot be used as a screening tool for fracture risk, it is becoming a powerful tool in helping to better understand changes in fragile bone.