The binding of two biomolecules viewed from the atomic level is highly complex. It involves the formation or removal of many individual non-covalent bonds both between the interacting molecules as well as with solvent. Currently, our understanding of the thermodynamic quantification of biomolecular interactions is somewhat naïve. ITC (isothermal titration calorimetry) provides a rapid route to a full thermodynamic characterization of a biomolecular interaction. Armed with these data, what are we really able to understand about complex formation and can any of this information provide a useful tool to aid drug development? Correlations between thermodynamic data and structural detail have been investigated, allowing insight into ways in which these can be used to understand protein-ligand interactions and provide input into the decision-making process in drug development.