With great efforts by Robinson and others, native mass spectrometry of protein complexes is now becoming a rapidly developing field in mass spectrometry.In this presentation,I am going to give a brief introduction about instrumentation and ionization methods in analysis of protein complexes by native mass spectrometry.I will also discuss applications of native mass spectrometry to top-down proteomics and to analysis of protein-protein and protein-ligand interactions.Using the mycobacterial metallothionien-metal ion complex as the example, I will show how native mass spectrometry is used to measure stoichiometry of protein-ligand complexes and biological functions of metallothionien.Recent studies also demonstrate that native mass spectrometry is a powerful approach to mapping intrinsic protein-ligand interactions and to evaluating the affinity of weakly-binding protein-ligand complexes.Despite of the technique challenges, native mass spectrometry has been successfully applied into the study of membrane proteins complexes.All together it shows that native mass spectrometry is a useful tool in drug screening and discovery, and in understanding of cellular protein machinery.