New, highly sensitive, biosensor concepts make it possible to assay biomacromolecules at concentrations that previously were far below the limit of detection. The previous generation of assays used in quality control situations during biotechnological production was designed primarily for monitoring target molecules, which typically appeared in high concentrations. Hence, novel analytical techniques with high sensitivity should become increasingly important in meeting the demands from regulatory agencies with regard to declaring levels of impurities in biopharmaceuticals. Such techniques also open up opportunities for a range of other challenging measurements, for example, in the area of biohazards. This review describes the development of immuno-based biosensors and exemplifies these by presenting analyses of common impurities in biopharmaceutical production.