Recent advances in mass spectrometry have rendered it an attractive and versatile tool in industrial and academic research laboratories. As a part of this rapid growth, a considerable body of literature has been devoted to the application of mass spectrometry in studies involving enantioselectivity, molecular recognition, and supramolecular chemistry. In concert with separation techniques such as capillary electrophoresis and liquid chromatography, mass spectrometry allows rapid characterization of a large array of molecules in complex mixtures. A majority of these findings have been made possible by the introduction of 'soft-ionization' techniques such as electrospray ionization interface. Other techniques such as atmospheric pressure chemical ionization mass spectrometry have been widely used as a rugged interface for quantitative liquid chromatography-mass spectrometry. Herein, we present a brief overview of the above techniques accompanied with several examples of enantioselective capillary electrophoresis- and liquid chromatography-mass spectrometry in drug discovery and development. Although the emphasis of this article is on quantitative enantiomeric chromatography-mass spectrometry, we envisage that similar strategies are adaptable in qualitative studies.