The most common pharmacophore building concepts based on either 3D structure of the target or ligand information are discussed together with the application of such models as queries for 3D database search. An overview of the key techniques available on the market is given and differences with respect to algorithms used and performance obtained are highlighted. Pharmacophore modelling and 3D database search are shown to be successful tools for enriching screening experiments aimed at the discovery of novel bio-active compounds.Section Editor:Hugo Kubiniyi – University of Heidelberg, GermanyPharmacophore models are hypotheses on the 3D arrangement of structural properties, such as hydrogen bond donar and acceptor properties, hydrophobic groups and aromatic rings of compounds that bind to a biological target. In the presence of the 3D structure of this target of by comparison with inactive analogs, further geometric and/or steric constraints can be defined. The article describes and evaluates strategies and commercial software for pharmacophore definition, starting from the 3D structures of ligand-protein complexes or from ligands alone. Once a pharmacophore model is established, 3D searches in large databases can be performed, leading to a significant enrichment of active analogs.