Identification of the receptor-bound conformation for a series of drugs activating the same receptor makes it possible to model the receptor cavity. A significant part of this chapter illustrates the importance of the 3D nature of the molecular recognition processes. The combinatorial nature of conformational possibilities implies computer-based molecular modeling as a necessary addition to the arsenal of multidisciplinary methods that the medicinal chemist has to apply in structure–activity studies and drug design. Prediction, synthesis, and testing are all significant in receptor mapping and pharmacophore identification. It has been noticed that topographical mapping of the volume of space available for steroid binding at the 3α,20β- hydroxysteroid dehydrogenase, a single enzyme with two activities, from streptomyces, bydrogenans was used to help design a suicide substrate for this enzyme. Some major applications of pharmacophore and receptor mapping include: opiate pharmacophore model, pancreatic glucoreceptor, and dopamine receptor. While the dynamic process of drug-receptor recognition probably involves multiple steps culminating in the activation of the receptor, it is possible to assume a unique arrangement of the electron density responsible for triggering the coupled response analogous to a transition state that is common to all drugs capable of activating that response. The concept of a pharmacophore and pharmacological evidence that a set of compounds interact with a unique receptor provides an opportunity to test different pharmacophores for consistency and possible uniqueness.