Methadone is a synthetic opioid, used both as an analgesic in severe pain relief and now mainly in the treatment of opiate dependence. Such use of the drug has increased as its advantages have become widely recognized. There are undesirable outcomes from its greater use, including a substantial market in diverted methadone and a high number of deaths where the drug has been implicated. It is important to understand how and why methadone causes death so that such fatalities can be minimized, and to disseminate such information. This paper presents an overview of the chief effects of methadone on the human body, considering its metabolism, drug interactions and tolerance. The principal mechanisms by which methadone causes death are discussed: respiratory depression, aspiration of vomit, pulmonary oedema, bronchopneumonia, cardiac problems and renal failure. Many such deaths are preventable, if drug interactions and polydrug use are avoided, its longer period of metabolism and individuals' tolerance levels are considered. It is hoped that this paper will (a) help guide health professionals in their management and treatment of patients participating in methadone treatment programmes, and (b) provide some basic information for those dealing with individuals who have consumed methadone. Copyright © 2004 John Wiley & Sons, Ltd.