Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) are the main techniques for studies at the interface of life sciences and chemistry. MS is mostly used due to its high sensitivity and wider spectral database, but the need for a specific standard for quantitative results and the intrinsic deficiency to provide unambiguous structural identification are limiting for its sole use for analysis. On the other hand, NMR is the most structurally informative analytical tool in organic chemistry and its capability as a direct quantitative detection brands it as an absolute detector. The complementary aspects of NMR and MS are obvious, and NMR disadvantages are related to its low sensitivity and poorly cataloged databases. The complexity presented by NMR spectra, resulting from the fact that a molecule produces more than one signal, can be reflected as an advantage, since these signals characterize structural particularities for the unequivocal identification of organic compounds. A wide variety of small molecule metabolites can be measured simultaneously in NMR. In fact, the only requirement for NMR signal detection is the presence of active nuclei (e.g. the 1 H isotope naturally occurring in 99.97%); solvent solubility for liquid-state NMR are also important requirements for high quality data. But the intense overlap of signals that occurs in complex mixtures in the NMR spectra can limit a complete qualification of the analyzed sample since each compound can present a very complex spectrum by itself. With the use of two-dimensional (2D) experiments, mainly those modulated by the chemical shift of C, there is an increase in the spectral window to 20 x 200 ppm which makes the overlap less likely, compared to the spectral window of 20 ppm in an NMR experiment of one-dimensional 1 H. In this sense, with the use of 2D experiments, in principle, it is possible to obtain chemical shift data of two interconnected nuclei for comparison with known database for matching, while, in one-dimensional (1D) experiments, the comparison is made using chemical shift data of only one type of nucleus. Similarly to the use of MS/MS data to assure compound annotation in MS, the orthogonal dimension in NMR can also be used to assure identification to organic compounds. This review aims to explore the main tools that are freely available for compound identification in mixtures using 2D NMR and to suggest a new pulse sequence that could be used for time-saving acquiring the spectral data required by these methods. This is meant to be a guide for research groups in the field of natural products and metabolomics to explore the available possibilities and the used data is accessible here (ZENODO at DOI: ). The demonstrations that follow were done using data from open repository and data collected from samples processed by the authors. Method descriptions for sample preparation are available at the Supplementary Information (SI.1)