This review describes modern mass spectrometric techniques which make it possible to apply to highly polar and large biomolecules. In recent years, the use of mass spectrometry has dramatically expanded in biochemical and medical fields. Significant developments in these techniques have been established by ESI/MS (electrospray ionization mass spectrometry) and MALDI-TOF/MS (matrix-assisted laser desorption ionization time-of-flight mass spectremetry). ESI can detect weak interactions such as cyclodextrin inclusion complexes, enzyme-substrate complexes, double stranded DNA and its intercalation with a ligand. It is expected to be a powerful tool for study of molecular recognition at the picomolar level. ESI can also be easily interfaced with liquid chromatography (LC/MS). On-line LC/MS is widely applicable for mixture analysis. MALDI-TOF provides extremely high sensitivity Such as sub picomolar level analysis. PSD-MS (post source decay-mass spectrometry) gives structural information, which is a technique similar to CID-MS/MS with extremely high sensitivity.