Semaphorins are key players in the control of neural circuit development. Recent studies have uncovered several exciting and novel aspects of neuronal semaphorin signalling in various cellular processes--including neuronal polarization, topographical mapping and axon sorting--that are crucial for the assembly of functional neuronal connections. This progress is important for further understanding the many neuronal and non-neuronal functions of semaphorins and for gaining insight into their emerging roles in the perturbed neural connectivity that is observed in some diseases. This Review discusses recent advances in semaphorin research, focusing on novel aspects of neuronal semaphorin receptor regulation and previously unexplored cellular functions of semaphorins in the nervous system.