Recent experimental and clinical research has demonstrated that opioids can produce potent and receptor-specific analgesic effects outside the central nervous system. Opioid receptors are localized on peripheral terminals of sensory nerves and their endogenous ligands, opioid peptides, have been discovered in immune cells within inflamed tissue. Many controlled clinical studies confirm the experimental data. These findings open up the exciting perspective of the development of an entirely novel generation of peripherally active opioid analgesics devoid of centrally mediated side effects.