In the vertebrate central nervous system (CNS), specialized glial and neuronal cells positioned at the dorsal and ventral midline act as intermediate targets for commissural axons by secreting a variety of attractants and repellents. Despite the diversity of commissural projections, recent findings suggest that the same basic set of molecules controls midline crossing at all level of the CNS. Midline crossing is associated with an important switch of the combinatorial expression of several axon guidance receptors on the growth cone of commissural axons. I will review here novel studies that reveal how the expression of these receptors and the activity of their ligands are modulated by transcriptional, translational, and post-translational modifications. This also uncovers extensive cross talks between axon guidance pathways.