The creation of artificial receptors remains an open challenge in supramolecular chemistry. In particular, the detection of small biomolecules in aqueous or complex biological media by supramolecular chemosensors proved difficult. Overcoming this hurdle would enrich many application areas such as diagnostics and metabolomics. In fact, the widely used antibody-based assays are generally not suitable for the detection of small, biogenic molecules or for real-time monitoring of metabolite concentration changes that are occurring in biological processes. We have developed a remarkably facile and versatile biomimetic strategy for the design of high-affinity artificial receptors by exploiting a combination of specific analyte-host interactions and the powerful, non-classical hydrophobic effect as driving forces for binding. Along this line of research, we are striving to deepen the fundamental understanding of the driving forces for aqueous self-assembly. Furthermore, we are introducing new concepts and methods that allows for the in situ differentiation of spectroscopically silent and structurally similar analytes, paving the way for differential sensing applications in complex media. Here, the “communication-based” sensing approach is the specialty of the group.Current developments include the monitoring of dynamic processes, e.g. of enzymatic reactions, and the extension of the sensors to applications in living cells.