The goal of the proposed workshop is to bring together worldwide experts in the field of molecular recognition and protein-ligand binding. The invited speakers will be selected based on their outstanding contributions to our understanding of molecular recognition and ligand association, focusing on two major research criteria: (a) work that provides new physical insight into the molecular recognition process and the driving forces determining thermodynamic signatures of binding and (b) recent methodological advances in applications to predicting and measuring protein-ligand binding observables. In particular, we will stimulate the presentation and discussion of the challenges posed by compensating enthalpic and entropic terms, competing solute and solvent contributions, and the relevance of complex configurational ensembles comprising multiple protein, ligand, and solvent intermediate states. As more complete physics is taken into account, computational approaches increase their ability to complement experimental measurements, by providing a microscopic, dynamic view of ensemble-averaged experimental observables. Physics-based approaches are increasingly expanding their power in drug discovery and design. Therefore, we propose to involve both experimental and computational scientists from industry and academia in a workshop spanning between theory and “real-life” applications.