1. Nociceptin/orphanin FQ (NC) and its receptor (OP4) represent a novel peptide/receptor system pharmacologically distinct from classical opioid systems. 2. Via OP4 receptor activation, NC regulates several biological functions, both at peripheral and central levels; therefore, the OP4 receptor may be viewed as a novel target for drug development. However, the pharmacology of this receptor is still in its infancy, with few molecules interacting selectively with this receptor. 3. In the present article, we review the findings of studies that have investigated the pharmacological profile of ligands selective for the OP4 receptor, these being two antagonists, the peptide [Nphe1]NC(1-13)NH2 and the non-peptide J-113397, and two agonists, the peptide [Arg14,Lys15]NC, and the non- peptide Ro 64-6198. 4. The results of these studies indicate that agents that selectively activate or block the OP4 receptor may represent new potential drugs for the treatment of human diseases.