Genetic analysis of nociceptive behaviors in the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster has led to the discovery of conserved sensory transduction channels and signaling molecules. These are embedded in neurons and circuits that generate responses to noxious signals. This article reviews the neurons and molecular mechanisms that underlie invertebrate nociception. We begin with the neurobiology of invertebrate nociception, and then focus on molecules with conserved functions in vertebrate nociception and sensory biology.