Stereochemical aspects of drug action have intrigued researchers ever since (and even before) the introduction of the receptor concept. Easson and Stedman first formalized this by suggesting the three-point tethering of an asymmetric ligand to its macromolecular target. Today, enantioselectivity is increasingly understood in molecular and atomic detail. Through site-directed mutagenesis, the amino acids responsible for the stereoselective recognition of ligand molecules have been identified in a number of cases, in particular for the b(2)-adrenergic receptor, a prototypic G protein-coupled receptor. Novel ligands with one or more chiral centers and complicated stereochemistry continue to be developed as potential medicines, despite reservations put forward by regulatory agencies. In this review, recent achievements in this respect will be discussed for a number of receptor (sub)families, and some general thoughts will be presented on the stereoselectivity of drug action.