Liquid Chromatography- Mass Spectrometry is a powerful analytical technique having high Sensitivity and Specificity. LC-MS combines the separation capabilities of Liquid Chromatography with the mass analysis capabilities of Mass Spectrometry. Liquid Chromatography separates the mixture, which is having multiple components, and then Mass Spectrometry provides the Spectral information which is used to identify each separated component. Interfaces are used in LC-MS system to transfer the maximum amount of analyte, remove a significant portion of the mobile phase, and preserves the chemical identity. Different types of Interfaces are used which include Atmospheric-Pressure Ionization, Electrospray Ionization, Atmospheric Pressure Chemical Ionization, Thermospray and Plasma Spray Ionization, Particle Beam Ionization, Continuous Flow Fast Atom Bombardment. LC-MS having a wide range of application in various field which include Pharmaceutical, Drug Development, Forensic Science, Cosmetic, Petrochemistry, Environment, Food Analysis, Biochemical Application. In this article Principle, Instrument and Application are discussed briefly.