In contrast to the classical approaches used for natural product identification, spectroscopic techniques such as liquid chromatography coupled with nuclear magnetic resonance (LC-NMR) offer robust and efficient approaches for the rapid dereplication of natural product extracts. This paper describes the modes of operation, resolution, sensitivity, limits of detection, and applications to natural product profiling of LC-NMR. Hyphenated techniques such as LC-NMR provide a great deal of preliminary information about the content and nature of the constituents of crude natural product extracts, which is critical when large numbers of samples need to be processed and the isolation of known compounds is to be avoided. With further improvement in sensitivity, on-line C(HP)LC-NMR in conjunction with C(HP)LC-MS and further to this, the double hyphenation of C(HP)LC-NMR-MS are likely to be used as the major tools for not only the analysis of natural products but also for problems encountered in genomics, proteomics and drug metabolomics.