The most widely used method for isotope analysis at natural abundance is isotope ratio monitoring by Mass Spectrometry (irm‐MS) which provides bulk isotopic composition in 2H, 13C, 15N, 18O or 34S. However, in the 1980s, the direct access to Site‐specific Natural Isotope Fractionation by Nuclear Magnetic Resonance (SNIF‐NMRTM) was immediately recognized as a powerful technique to authenticate the origin of natural or synthetic products. The initial – and still most popular – application consisted in detecting the chaptalization of wines by irm‐2H NMR. The approach has been extended to a wide range of methodologies over the last decade, paving the way to a wide range of applications, not only in the field of authentication but also to study metabolism. In particular, the emerging irm‐13C NMR approach delivers direct access to position‐specific 13C isotope content at natural abundance. After highlighting the application scope of irm‐NMR (2H and 13C), this article describes the major improvements which made possible to reach the required accuracy of 1‰ (0.1%) in irm‐13C NMR. The last part of the manuscript summarizes the different steps to perform isotope analysis as a function of the sample properties (concentration, peak overlap) and the kind of targeted isotopic information (authentication, affiliation). Copyright © 2016 John Wiley & Sons, Ltd.