One of the major challenges of the post-genomic era is the rapid characterisation of protein structure. High-throughput structural genomic projects involving X-ray crystallography and NMR spectroscopy are in progress to solve the three-dimensional structures of a large of number of proteins. These techniques have their advantages and disadvantages and cannot be applied to study all proteins, giving sufficient opportunity for other techniques to also a play significant role in proteomics research. Fourier transform infrared (FTIR) spectroscopy is one of the techniques that has gained popularity in this area since measurements on small quantities of proteins can be carried out very rapidly in various environments. However, there is a need for improvements in the interpretation of protein FTIR infrared spectra and development of methods for accurately quantifying protein secondary structure from infrared spectra of proteins. Over the years, much progress has been made in this area and here we provide an overview of the major progress made so far, along with their strengths and weaknesses. The particular focus of the Chapter is on methods used for quantitative prediction of secondary structure from infrared spectra.