Functional neural circuits depend on the establishment of specific connections between neurons and their target cells. To this end, many axons have to travel long distances to reach their target cells during development. Studies addressing the molecular mechanisms of axon guidance have to overcome the complexity of subpopulation-specific requirements with respect to pathways, guidance cues, and target recognition. Compared to the brain, the relatively simple structure of the spinal cord provides an advantage for experimental studies of axon guidance mechanisms. Therefore, the so far best understood model for axon guidance is the dI1 population of dorsal interneurons of the spinal cord. They extend their axons ventrally towards the floor plate. After midline crossing, they turn rostrally along the contralateral floor-plate border. Despite the fact that the trajectory of dI1 axons seems to be rather simple, the number of axon guidance molecules involved in the decisions taken by these axons is bewildering. Because guidance molecules and mechanisms are conserved throughout the developing nervous system, we can generalize what we have learned about the navigation of the floor plate as an intermediate target for commissural axons to the brain.