Abstract: The development of the eletrospray ionization mass spectrometry (ESI-MS) technique allows itself to be a useful tool in studying noncovalent complexes. The use of ESI-MS for the probe of noncovalent interactions involved in supramolecules has been a fast growing area of research over the past few years. This article reviews some of the highlights involving the application of the eletrospray ionization mass spectrometry for solving problems in the area of noncovalent interactions, such as binding selectivity, binding constant, binding sites and chiral recognition. Some important factors in the related experiments are also discussed.