Previous studies have led to the suggestion that the midline of the developing Drosophila central nervous system might serve a dual function during growth cone guidance, providing attractive signals for those growth cones that project across the midline, and at the same time repulsive signals for those growth cones that stay on only their own side. In an attempt to discover some of the genes encoding key components of these two guidance systems, we performed a large-scale screen in Drosophila for mutants that affect the development of the axon commissures. Here we review the mutant phenotypes of two new genes in which either too few (commissureless) or too many (roundabout) growth cones cross the midline. These phenotypes suggest that these two genes encode important components for growth cone guidance at the midline.