Forebrain neurosecretory systems are widespread in the animal kingdom. This review focuses on recent molecular data from protostomes, discusses the original complexity of the bilaterian forebrain neurosecretory system, provides an evolutionary scenario for the emergence of the vertebrate preoptic area/hypothalamus/neurohypophysis and suggests a possible function for an ancient set of sensory-neurosecretory cells present in the medial neurosecretory bilaterian forebrain.