Nuclear magnetic resonance spectroscopy (NMR) is essential for the de novo structure identification of natural products. This technique can be directly or indirectly hyphenated to high performance liquid chromatography (HPLC) leading to efficient LC-NMR platforms. NMR is, however, a very insensitive detection method compared to mass spectrometry and several strategies for its efficient hyphenation with HPLC have been developed. This includes on-line LC-NMR, SPE-NMR, or other at-line approaches involving microflow probes or microtubes in combination with cryoprobes. All of these various technologies and their potentials and limitations in the field of natural product research are described. Recent applications involving other complementary detection methods such as LC-MS or biological HPLC profiling illustrate its utilization.