The metabolome is composed of a vast number of small-molecule metabolites that exhibit a diversity of physical and chemical properties and exist over a wide dynamic range in biological samples. Multiple analytical techniques, used in a complementary manner, are required to achieve high coverage of the metabolome. MS is playing a central role in metabolomics research. Herein, we present a brief overview of the MS-based technologies employed for high-throughput metabolomics. These technologies range from chromatography-MS techniques, such as GC-MS and LC-MS, to chromatography-free techniques, such as direct infusion, matrix-assisted and matrix-free laser desorption/ionization, imaging and some new ambient ionization approaches. Chemoinformatics and bioinformatics tools are widely available to facilitate successful metabolomics studies by turning the complex metabolomics data into biological information through streamlined data processing, analysis and interpretation.