Biochemical processes in living organisms rely on a plethora of molecular reactions and interactions involving chiral molecules, and these processes often show different responses to the enantiomers of exogenous or endogenous chemicals. The interaction of enantiomeric drugs with a target receptor is a paradigmatic example of chirality effects on general biological action and is directly related to the formation of a drug-receptor supramolecular complex. In particular the drug-receptor model can be used to explore the relation of chirality to at least three important issues encountered in supramolecular chemistry: complementarity, preorganization, and (enantio)selectivity. A detailed understanding of those factors governing enantioselectivity of biological receptors is facilitated by the study at molecular level of model systems with simplified structures that are amenable to physico-chemical investigations. Liquid chromatography on chiral stationary phases offers the opportunity to study enantioselective interactions between surface immobilized chiral selectors, viewed as minimalist mimics of macromolecular receptors, and a large set of chiral guests, under a variety of experimental conditions. Indeed, for a significant number of systems, close agreement has been found between retention data gathered by chromatography and association constants measured by spectroscopy in free solution. Chiral supramolecular selectors featuring highly preorganized, medium-sized macrocyclic structures are attractive in this context because they often afford high levels of enantioselectivity and yet have relatively low molecular complexity, thus facilitating the understanding of operative enantioselective recognition mechanisms from easily collected chromatographic data. In the present chapter we first illustrate the general principles of supramolecular chemistry and their integration into the design of liquid chromatographic systems, with particular focus on enantioselective variants based on chiral macrocyclic selectors of natural or synthetic origin. In the second part we discuss the elaboration of enantioselective recognition models from chromatographic data and how these models can be extended to and studied with non-chromatographic systems (free solution by nuclear magnetic resonance, gas phase by mass spectrometry).