Failing to explicitly account for conformational entropy in structural biology skews our understanding of thermodynamics, hindering our ability to harness this source of free energy. Conformational entropy modulates free energy through three main mechanisms: entropic pre-payment, spatial entropic redistribution, and the catalytically competent ensemble. However, the lack of widespread structural ensemble representations limits our ability to explicitly explain the contributions of entropy and leverage this driving force for the prospective design of function . Conformational ensembles, grounded in experimental data, will allow entropy to be integrated with probabilistic accounting of enthalpic-dominated interactions such as hydrogen bonds, salt bridges, and hydrophobic contacts to ground the complex interplay between structure, dynamics, and function in thermodynamics.