1. Opioids, in one form or another, have been used for their pain-relieving properties from prehistoric times: they are still the first line medication for the treatment of severe nociceptive pain and are likely to remain so for the foreseeable future. 2. The therapeutic index of opioids used for pain management is low: opioid side effects are essentially extensions of therapeutic effects and no available agent has a marked advantage over the others. When used for opioid 'anaesthesia', differences in therapeutic index are more obvious due to differences in non-opioid effects. 3. Opioid receptors in brain and spinal cord periphery are the main 'therapeutic targets' and clinical dosage strategies have been derived using a variety of systemic (indirect or blood-borne) methods as well as intraspinal and intracerebroventricular (direct) methods: no method, however, is without potential side effects. Peripheral opioid effects are now being exploited with intra-articular injection. 4. Opioid pharmacokinetics and pharmacodynamics are characterized by high inter-subject variability: accordingly, patient-controlled dosage strategies are found to be more successful for pain control than deterministic recipes.