The genetic systems controlling body axis formation trace back as far as the ancestor of diploblasts (corals, hydra, and jellyfish) and triploblasts (bilaterians). Comparative molecular studies, often referred to as evo-devo, provide powerful tools for elucidating the origins of mechanisms for establishing the dorsal-ventral and anterior-posterior axes in bilaterians and reveal differences in the evolutionary pressures acting upon tissue patterning. In this Review, we focus on the origins of nervous system patterning and discuss recent comparative genetic studies; these indicate the existence of an ancient molecular mechanism underlying nervous system organization that was probably already present in the bilaterian ancestor.