Pain perception and appropriate behavioral responses are important for survival. The conservation of the opioid ligand and receptor suggests evolution of opioid receptors mediating antinociception throughout vertebrate phylogeny. Fish, amphibians, and reptiles have appropriate neurologic components, display the appropriate behavior in response to a painful stimulus, and possess antinociceptive mechanisms to modulate pain. Because pain perception in these species is therefore likely to be analogous to that of mammals, invasive and painful procedures should always be accompanied by appropriate analgesia and anesthesia. Although specific doses have not been established in clinical trials, clinicians should attempt to provide lower vertebrates with appropriate analgesia during painful procedures. Further experimental and clinical investigations are necessary to expand the current veterinary literature in the area of pain and analgesia in lower vertebrates such as fish, amphibians, and reptiles.