Opioid receptors, which evolved ∼450 million years ago, are the targets of endogenous opioid peptides and opiate drugs. Opioids and their receptors have been studied in many species, including fishes and especially, the zebrafish. The opioid peptides are encoded by four precursor genes named proenkephalin, prodynorphin, proopiomelanocortin, and pronociceptin. The four types of opioid receptors, μ (MOR), δ (DOR), κ (KOR), and the nociceptin opioid receptor (NOP), have been classified based primarily on pharmacological criteria.