A brief historical overview of the concept of allosteric interaction is presented together with the different kinds of allosteric control recognized, in the past decades, with the model system of pentameric ligandgated ion channels. Multiple levels of allosteric modulation are identified that include sites distributed in the extracellular ligand binding domain (e.g. Ca2+ or benzodiazepines), the transmembrane domain (e.g. general anesthetic and various allosteric modulators) and the cytoplasmic domain, as potential targets for drug design. The new opportunities offered by the recent technological developments are discussed.