Providing a general introduction to the use of isotope dilution mass spectrometry (IDMS) technique for high accuracy measurements, this guide describes two specific methodologies for applying the technique. These methodologies, one for inorganic mass spectrometry and the other for organic mass spectrometry, have been developed and tested through a series of collaborative studies carried out by a sub-committee of The Royal Society of Chemistry’s Analytical Methods Committee. The isotope dilution mass spectrometry (IDMS) technique is well known, however, its application can present considerable difficulties and without extensive development for a specific application may well give less accurate data than conventional calibration. Produced jointly by the Royal Society of Chemistry’s Analytical Methods Committee and the Valid Analytical Measurement (VAM) programme, the aim of this volume is to provide a simplified yet robust methodology, together with adequate guidance, to enable laboratories wishing to use the technique to obtain reliable data. The methodologies, for inorganic and organic mass spectrometry, which use exact and approximate matching, are illustrated with worked examples and clear diagrammatic representations.