Changing paradigms of health care and increasing knowledge of opioid addiction continue to influence the attitudes of the health profession toward methadone maintenance treatment (MMT). This approach has again reached the forefront of attention because of its significant role in reducing HIV transmission associated with intravenous drug use. In spite of the well-documented benefits of MMT, patients continue to detoxify from methadone for a variety of reasons both overt and covert. Variable outcomes and generally poor long-term abstinence rates results. At present uncertainty still exists surrounding who should attempt detoxification, when or how this should be done, or whether in fact detoxification should be attempted at all. This article describes and examines factors that are positively and negatively associated with detoxification outcome. Evidence for the interrelationship of two notably significant determinants, affective states and protracted withdrawal, are presented and discussed as they relate to theories of relapse and outcome.