Axonal growth cones navigate long distances along specific pathways to establish complex patterns of neuronal connections. A growing number of signals have been identified that participate in these steering decisions. This review will concentrate on a large and growing family of chemorepellents, the semaphorins. This family contains both secreted and membrane-bound proteins expressed in many neuronal and non-neuronal tissues of invertebrates and vertebrates. Ongoing studies have given us a better understanding of how their highly conserved signalling system is involved in patterning neuronal connections.