The current developments in liquid chromatography-mass spectrometry (LC-MS) and its applications to the analysis of pharmaceuticals are reviewed. Various mass spectrometric techniques, including electrospray and nanospray ionization, atmospheric pressure chemical ionization and photoionization and their interface with liquid chromatographic techniques are described. These include high performance liquid chromatography, capillary electrophoresis and capillary electrochromatography and the advantages and disadvantages of each technique are discussed. The applications of LC-MS to the studies of in vitro and in vivo drug metabolism, identi?cation and characterization of impurities in pharmaceuticals, analysis of chiral impurities in drug substances and high-throughput LC-MS-MS systems for applications in the “accelerated drug discovery” process are described. Liquid chromatography-mass spectrometry (LC-MS) is an analytical technique that couples high resolution chromatographic separation with sensitive and speci?c mass spectrometric detection. This includes high performance liquid chromatography (HPLC)-MS, capillary electrophoresis (CE)-MS and more recently capillary electrochromatography (CEC)-MS. The technique is still fast developing, particularly in the mass spectrometry area, with vastly improved sensitivity and resolution. It is probably the most powerful technique currently available for pharmaceutical analysis. This review is intended as a discussion on the current developments of LC-MS in pharmaceutical analysis rather than a review of literature alone. Various LC-MS techniques will be described brie?y and the advantages and disadvantages of each will be discussed. Brief History of LC-MS The last twenty years has seen a dramatic increase in the capabilities of MS. At the beginning of this period the invention of fast atom bombardment (FAB), by Barber et al. in 1981,1) enabled easier analysis of involatile and thermally unstable molecules, especially those of biological interest. It may be argued that this technique acted as a catalyst for the development of other ionization techniques, such as matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI), applicable to such molecules. Atmospheric Pressure Ionization (ESI and APCI) Over the last decade, ESI and atmospheric pressure chemical ionization (APCI), have become the dominant techniques su- perseding thermospray etc. and are likely to remain so for the foreseeable future being inherently the most suitable for analytes in solution presented to the MS. ESI was originally proposed by Dole,9) who suggested using charged droplets as a source of ions for MS and Fenn10) pioneered its development as an ionization source for MS, leading to the ?rst commercially available instrument in 1989.