This lecture illustrates the early stages in the planning and discovery of propranolol, an adrenaline β-adrenergic receptor antagonist, and cimetidine, a histamine H 2 -receptor antagonist—the first examples of clinically useful drugs from each of these classes. The significance of selective agonists, partial agonists, and syntopic antagonists and the importance of the bioassay and the use of molar models in the drug discovery process are discussed. For the future, an outline of potential developments in hormone-receptor concepts is offered leading to the conclusion that progress may depend on improvements in bioassays and related molar modeling.