Adhesion GPCRs (aGPCRs) form a subfamily of the large GPCR super family. Most aGPCRs are characterised by a non-covalent bipartite structure that consists of a large extracellular domain and a membrane-spanning 7 transmembrane domain. Typically, aGPCRs can combine cell adhesion by the large extracellular domain with intracellular signalling by the 7 transmembrane domain. Immune responses rely on cellular communication and subsequent defence reactions. Indeed, aGPCR ADGRB1 and members of the ADGRE class have been linked to processes like phagocytosis, leucocyte activation and migration. Nevertheless, research is hampered by absence of endogenous ligands, unknown activity of generated antibodies and non-identified signalling pathways. Yet, based on their membrane localisation and important function, aGPCRs could be novel drug targets to modulate leucocyte function.