The development of electrospray ionization coupled to mass spectrometry has enabled the analysis of very large intact protein complexes, even when they are held together by weak non-covalent interactions. Together with equally spectacular advances in mass spectrometric instrumentation, a new field has emerged, termed native protein mass spectrometry, which focuses on the structural and functional analysis of the dynamics and interactions occurring in protein complexes. In the past two years, several important progressive steps in technologies have been reported that have led to exciting applications ranging from the detailed study of equilibria between different quaternary structures as influenced by environmental changes or binding of substrates or cofactors, to the analysis of intact nano-machineries, such as whole virus particles, proteasomes and ribosomes.