Methadone is emerging as a good choice for the management of chronic non-cancer pain both as a first line medication and as a replacement opioid. Particular cautions must be observed as methadone's pharmacokinetics and pharmacodynamics are unique among opioids. Milligram for milligram, methadone is much more powerful than morphine; ... there is significant interindividual variability in the response to methadone. In the initiation of chronic opioid therapy with methadone or the transition from a different opioid, careful day-to-day monitoring is essential. Furthermore, methadone has potential to interact with a large number of medications, and drug-drug interactions must be considered. Finally, compared with other opioids, methadone can offer a very significant cost advantage.