we use a straightforward approach based on potential of mean force calculations from explicit solvent molecular dynamics simulations to derive complete thermodynamic signatures of cavity-ligand binding. using extensive sampling, free energy, enthalpy, and entropy estimates are obtained along the binding coordinate for a set of systems with varying cavity and ligand physicochemical properties, thus revealing an unprecedented, nanoscale picture of hydration thermodynamics. despite the simplicity of the model systems considered, a broad range of thermodynamic signatures is found in which water (rather then cavity or ligand) contributions appear to largely determine the overall system enthalpy-entropy compensation.