Mass spectrometry (MS) and nuclear magnetic resonance (NMR) have evolved as the most common techniques in metabolomics studies, and each brings its own advantages and limitations. Unlike MS spectrometry, NMR spectroscopy is quantitative and does not require extra steps for sample preparation, such as separation or derivatization. Although the sensitivity of NMR spectroscopy has increased enormously and improvements continue to emerge steadily, this remains a weak point for NMR compared with MS. MS-based metabolomics provides an excellent approach that can offer a combined sensitivity and selectivity platform for metabolomics research. Moreover, different MS approaches such as different ionization techniques and mass analyzer technology can be used in order to increase the number of metabolites that can be detected. In this chapter, the advantages, limitations, strengths, and weaknesses of NMR and MS as tools applicable to metabolomics research are highlighted.