AbstractPharmacophores describe the spatial arrangement of essential interactions in a receptor‐ligand complex. Although highly established in ligand‐based virtual screening, the application of pharmacophores for in absence of a ligand is more sophisticated. This article summarizes the recent approaches to derive and evaluate pharmacophore models using only limited information (e.g. a homology model of the binding site). A range of different methodologies including geometrical and/or potential‐based methods and successes in the application to virtual screening problems are described. Advantages and current limitations of the state‐of‐the‐art methods and future perspectives for development are discussed in this publication.