Our understanding of how axons find their targets during neural development has advanced markedly over the past decade. We now know of many families of guidance cues that include members capable of attracting or repelling advancing growth cones, and many of the receptors that mediate responses to these cues have been discovered. Indeed, the recent sequencing of the human genome underscores that, despite the existence of many novel proteins with the potential to function as guidance cues, we have already identified a surprisingly large repertoire of proteins that participates in the establishment of several well-characterized axon trajectories. A range of model systems exploiting a variety of cellular and genetic paradigms are currently being employed successfully to understand the signaling events initiated by these guidance cues and their receptors that ultimately result in directed alterations of the growth cone cytoskeleton. However, what we lack at present is an understanding of how this great diversity of guidance information is interpreted at the level of a single advancing growth cone. It is not all that satisfying to assume for all guidance decisions that neuronal growth cones continuously integrate steering responses to attractants and repellents. There are several situations where opposing guidance cues, sometimes at very close range, would be likely to confuse growth cone responses, especially when intermediate attractive targets are reached and then left behind during the normal course of establishing a complex neuronal pathway.