Abstract: A new generation of multi-collector isotope ratio mass spectrometers is now capable of measuring isotope ratios with extremely high precision for non-traditional isotope system. As a result, the application of non-traditional isotope system on geology, environmental science, oceanography, medicine and other fields is developing rapidly. However, as there is still lack of the related isotope primary/standard reference in metrology, it causes a key problem in terms of how to obtain reliability and comparability of measurement results for non-traditional isotopes applied research. Therefore, researching, developing and promoting the use of accurate and reliable isotope CRMs are a key element for underpinning a good application of non-traditional isotope system. This article reviews the main problems of the isotope measurement, R&D status and development trend related to the non-traditional isotopes. The emphasis is on raising the understanding for the importance of R&D and use the isotope CRMs, promoting the well development of isotopic metrology standards and insuring the fully playing the role of its measurement traceability.