Infrared spectroscopy can provide insight into protein structure. This technique is sensitive to the backbone amide arrangement of peptide and protein molecules. In many cases, complementary as well as more expansive information is obtained as opposed to information obtained by other methods that examine the molecule's environmental surroundings, require molecular probes, or perhaps cannot investigate the molecule in its native environment. The foundation for spectroscopic differences between the various secondary structures arises not only from geometrical differences and hydrogen bond variations but also transition dipole coupling between neighboring oscillators. Theoretical predictions of protein spectra have been made using normal mode analysis and combined with experimental data. At present the amide I band has provided the most insight into secondary structure. Even more convincing results are obtained when both H2O and D2O are used as solvents. Recent advances in computerized technology and mathematical techniques have expanded the potential contributions of infrared spectroscopy in the area of protein structural determination. However, the limitations of resolution enhancement and curve-fitting techniques must be taken into consideration. The parameters must be carefully and optimally chosen and evaluated on a case-by-case basis. The subjectivity of these techniques makes a thorough understanding of the algorithms necessary, especially those commercially available. Infrared spectroscopy continues to provide insight into protein and peptide structures under biologically relevant conditions that enable the structure-function relationships for such molecules to be better understood.