Nociceptin was discovered at the end of 1995. It is the endogenous ligand of opioid receptor like 1 (ORL1 or LC 132) receptor. It plays an important role in pain modulation, cardiovascular system, ion channel, dependence and tolerance, learning and memory, etc. It is becoming a new research field to investigate the structure-activity relationship of ORL1 receptor and its ligands in recent years. Now, the studies on NC fragments, agonists, partial agonists, and antagonists that were found in the course of investigating the structure-activity relationship of nociceptin are reviewed.