To assess the general trends of entropic spatial redistribution after ligand binding, we identified ~700 pairs of high resolution X-ray crystal structures where the only difference was the presence of a small molecule ligand. We then re-built multiconformer models containing well-supported alternative conformations into the experimental data. These models allow us to estimate crystallographic order parameters for each model and compare the conformational entropy change upon ligand binding . A striking finding emerges from this analysis: the conformational entropy lost at the binding sites is correlated to the entropy gained at distal sites. We also observed diversity in the amount of entropy redistributed based on both the protein and ligand involved. Even for a single receptor, different ligands result in distinct patterns of entropy redistribution. Two ligands that cause equivalent reductions in entropy in the active site can differ by ~±1-2 kcals in the response at distal sites. This difference can occur because the ligands will engage different parts of the binding site in specific interactions that induce distinct patterns of spatial entropic redistribution. For example, in the kinase CDK2, the patterns of entropy in Type I inhibitors, which bind to the active-like conformation, are more similar to other Type I inhibitors than they are to Type II inhibitors, which bind to an inactive-like conformation. Similarly, Type II inhibitors were more similar to each other than they were to Type I inhibitors. However, even within the Type I inhibitors, ligands still showed unique patterns of conformational entropy, highlighting the possibility of designing for these features. The potential for tuning ligand properties to redistribute entropy also is evident across the entire dataset. Ligands with more specific and oriented interactions (e.g. hydrogen bonds) lead to greater local reductions in entropy and those binding events driven by apolar ligands lead to lower local reductions in entropy. Critically, these observations of spatial entropic redistribution are due to small, distributed changes in side chain alternative conformations and harmonic motions (B-factors), which are less well captured by traditional, single state structural models. This example highlights the critical importance of modeling the conformational ensemble to move towards a predictive understanding of the contributions of conformational entropy to ligand binding.