The on-line combination of liquid chromatography and mass spectrometry with the atmospheric-pressure ionization makes possible operation in both normal-phase and reversed-phase systems practically without limitation of flow rate and composition of the mobile phase, even under gradient-elution conditions. In the contemporary HPLC/MS systems, atmospheric pressure ionization techniques (APCI and electrospray) and thermospray ionization are most popular. The continuous-flow fast atom bombardment (CF FAB) is less frequent as it is limited to lower acceptable flow rates of mobile phase or particle-beam interface with the classical electron ionization (EI). In addition to the determination of molecular weights and structure information of sample components, this coupled method makes possible, from the HPLC point of view, a highly selective and sensitive detection.