The histamine H3 receptor was discovered 15 years ago, and many potent and selective H3 receptor agonists and antagonists have since been developed. Currently, much attention is being focused on the therapeutic potential of H3 receptor ligands. In this review, Rob Leurs, Patrizio Blandina, Clark Tedford and Henk Timmerman describe the available H3 receptor agonists and antagonists and their effects in a variety of pharmacological models in vitro and in vivo. The possible therapeutic applications of the various compounds are discussed.