Ligand-protein and protein-protein interactions play a pivotal role in any cellular process and function by means of complex and dynamic mechanisms that involve sophisticated intra- and intermolecular communication pathways. The deeper understanding of the molecular and structural mechanisms of these pathways of chemical information transfer constitutes the foundations of rational druggable target discovery and drug design. In this context the role of both molecular recognition/communication between the interacting partners and their quantitative/dynamic description constitute the crucial point. In this respect, many approaches at different level of complexity have been developed and applied to different druggable target like enzymes, membrane receptors and protein assembly. They mainly differ in the accuracy and resolution level of molecular description and, hence, in the derived quantitative molecular descriptors/predictors and ligand-target models. In this review, we will try to illustrate some selected examples of ligand-target receptor protein models, by comparatively considering both series of ligands (ligand-based communication modeling) and ligand-target complexes (target-based communication modeling) in order to describe the relevant structural/dynamic features of chemical information transfer in the ligand/drug design endeavour.