Professor David H. Russell has made seminal contributions in the area of structural mass spectrometry, viz. the development and application of mass spectrometry and ion mobility-mass spectrometry (IM-MS) for studies of gas- and solution-phase peptide/protein structure to address important questions underlying the rapidly developing area of MS-based structural biology. His studies of the conformational heterogeneity of peptides and proteins have attracted much attention because they are directly related to important questions concerning structural-MS as well as long-standing biophysical chemistry questions. These studies include cis/trans orientations of polyprolines, which have provided new levels of understanding of the effects of hydration on peptide/protein folding, development of cryo-IM-MS to explore the effects of hydration on peptide/protein structure, and the development of new experimental platform that make possible studies of water-mediated bio-molecule self-assembly reactions. Most recently, his research group has developed variable-temperature (1–100 oC)-ESI IMS/MS for studies of both cold- and heat-induced protein-ligand interactions. This approach investigates solution phase-protein folding/refolding reactions as well as structure, dynamics and stabilities of protein complexes, including folding chaperones, specifically GroEL. Collectively, these studies are becoming increasingly important as they potentially provide new approaches to investigate structure-function relationships of biological molecules.