The neuropeptide nociceptin, also called orphanin FQ (N/OFQ), is the endogenous agonist of the N/OFQ peptide receptor (NOP receptor). Both N/OFQ and the NOP receptor share a high degree of homology with classical opioid peptides and opioid receptors, respectively, and use similar signal transduction pathways as classical opioids. The NOP receptor has thus been regarded as the fourth member of the opioid receptor family. Despite this close relationship, 7 years of research have demonstrated that the N/OFQ system has a distinct pharmacological profile and serves different physiological functions. In particular, its role in the control of pain and analgesia at different levels of integration appears quite different from that of classical opioids. The recent development of specific antagonists at the NOP receptor and of NOP receptor or N/OFQ precursor knock-out mice have generated new insights into the role of N/OFQ in pain processing and help to evaluate the N/OFQ-NOP system as a potential target for new analgesic drugs.