Two embryonic cell populations, the neural crest and cranial ectodermal placodes, between them give rise to many of the unique characters of vertebrates. Neurogenic placode derivatives are vital for sensing both external and internal stimuli. In this speculative review, we discuss potential developmental and evolutionary relationships between two placode series that are usually considered to be entirely independent: lateral line placodes, which form the mechanosensory and electroreceptive hair cells of the anamniote lateral line system as well as their afferent neurons, and epibranchial placodes (geniculate, petrosal and nodose), which form Phox2b+ visceral sensory neurons with input from both the external and internal environment. We illustrate their development using molecular data we recently obtained in shark embryos, and we describe their derivatives, including the possible geniculate placode origin of a mechanosensory sense organ associated with the first pharyngeal pouch/cleft (the anamniote spiracular organ/amniote paratympanic organ). We discuss how both lateral line and epibranchial placodes can be related in different ways to the otic placode (which forms the inner ear and its afferent neurons), and how both are important for protective somatic reflexes. Finally, we put forward a highly speculative proposal about the original function of the cells whose evolutionary descendants today include the derivatives of the lateral line, otic and epibranchial placodes, namely that they produced sensory receptors and neurons for Phox2b-dependent protective reflex circuits. We hope this review will stimulate both debate and a fresh look at possible developmental and evolutionary relationships between these seemingly disparate and independent placodes. J. Exp. Zool. (Mol. Dev. Evol.) 310B:370–383, 2008. © 2007 Wiley-Liss, Inc.