Four papers in this issue of Nature present the long-awaited high-resolution crystal structures of the four known opioid receptors in ligand-bound conformations. These G-protein-coupled receptors are the targets of a broad range of drugs, including painkillers, antidepressants, anti-anxiety agents and anti-addiction medications. Brian Kobilkas group reports the crystal structure of the -opioid receptor bound to a morphinan antagonist and the dgr;-opioid receptor bound to naltrindole. Raymond Stevens group reports on the kgr;-opioid receptor bound to the selective antagonist JDTic, and the nociceptinorphanin FQ receptor bound to a peptide mimetic. In an associated News and Views, Marta Filizola and Lakshmi Devi for research on the mechanisms underlying receptor function and drug development. Cover: Universal Images GroupGetty Images.