At a fundamental level, biological processes are most often controlled using molecular recognition by proteins. Protein-ligand interactions impact critical events ranging from the catalytic action of enzymes, the assembly of macromolecular structures, complex signaling and allostery, transport phenomena, force generation and so on. The physical origin of high affinity interactions involving proteins continues to be the subject of intense investigation. Conformational entropy represents perhaps the last piece of the thermodynamic puzzle that governs protein structure, stability, dynamics and function. The presence and importance of internal conformational entropy in proteins has been debated for decades but has resisted experimental quantification. Over the past few years we have introduced, developed and validated an NMR-based approach that uses a dynamical proxy to determine changes in conformational entropy. This new approach, which we term the NMR "entropy meter," requires few assumptions, is empirically calibrated and is apparently robust and universal. Using this "entropy meter," it can now be quantitatively shown that proteins retain considerable conformational entropy in their native functional states and that this conformational entropy can play a decisive role in the thermodynamics of molecular recognition by proteins. Recent results show that changes conformational entropy of a protein upon binding a high affinity ligand is highly system specific and can vary from strongly inhibiting to even strongly promoting binding and everything in between. Thus one cannot possibly understand comprehensively how proteins work without knowledge of the breadth and underlying principles of the role of conformational entropy in protein function.  This approach also allows for the refinement of empirical coefficients that relate changes in accessible surface area to changes in the entropy of water and the determination of the loss of rotational-translational entropy in high affinity protein complexes. Supported by the NIH and the Mathers Foundation.