All multicellular organisms are highly dependent on the capacity developed by their cells to communicate with each other and with their environment. G protein-coupled receptors (GPCRs) play a fundamental role in controlling this communication. These seven transmembrane receptors regulate numerous physiological mechanisms in health and disease and thus, bear an immense pharmacological potential. One class of to date enigmatic GPCRs are Adhesion GPCRs. Despite their essential functions in several biological processes and their unique architecture facilitating cell and matrix interactions, Adhesion GPCRs are by far the most poorly understood receptor class. We use C. elegans to understand the roles of Adhesion GPCRs in development and neurobiology. Secondly, we are elucidating their modes of signaling and the pathways they are involved in to link physiological functions with molecular mechanisms.