In principle, Raman spectroscopy has the potential to answer many of the questions pertaining to the chemical detail of enzyme mechanisms. However, its application has been held back by the twin difficulties of lack of sensitivity and selectivity for large macromolecular complexes. This review addresses the development of the technique over the past 25 years to overcome these handicaps. Due to technical innovations, the Γeld stands at the brink of being applicable to a much wider range of enzyme systems ; high-throughput spectrographs coupled with red excitation are improving sensitivity and eliminating many of the problems formerly encountered with the interfering Γuorescence background. The advantages and disadvantages of resonance Raman and Raman di β erence spectroscopy for studying enzyme complexes are outlined. For a relatively few systems, unique information has been obtained in the areas of precise substrate geometries in functioning intermediates, on active site-to-substrate hydrogen bonds and on probing the strong electrostatic forces that can drive catalysis. These studies are detailed, with emphasis on how they provide powerful insight on enzyme mediated catalysis. With the improvements due to technical advances, the impact of these kinds of insights will soon be felt across the whole Γeld of enzymology.