Eph receptor Tyr kinases and their membrane-tethered ligands, the ephrins, elicit short-distance cell–cell signalling and thus regulate many developmental processes at the interface between pattern formation and morphogenesis, including cell sorting and positioning, and the formation of segmented structures and ordered neural maps. Their roles extend into adulthood, when ephrin–Eph signalling regulates neuronal plasticity, homeostatic events and disease processes. Recently, new insights have been gained into the mechanisms of ephrin–Eph signalling in different cell types, and into the physiological importance of ephrin–Eph in different organs and in disease, raising questions for future research directions.