Biosensors are analytical devices that use a biological or biologically derived material immobilized at a physicochemical transducer to measure one or more analytes. Although there are a large number of reviews on biosensors in general, there has been little systematic information presented on the application of natural receptors in sensor technology. This perspective discusses broadly the fundamental properties of natural receptors, which make them an attractive option for use as biorecognition elements in sensor technology. It analyses the current situation by reference to typical examples, such as the application of nicotinic acetylcholine receptor and G protein-linked receptors in affinity sensors and analyses the problems that need to be resolved prior to any commercialization of such devices.