The German Betäubungsmittelverschreibungsverordnung BtmVV (prescription regulation of narcotics), 5 part 2, 01 July 2001 commissioned the German Medical Association to establish guidelines on methadone maintenance therapy according to the medical-scientific state of the art. A joint commission of the German Medical Association and the National Association of Statutory Health Insurance Physicians developed guidelines for substitution therapy of opiate dependence which were adopted by the board of the German Medical Association in March 2002 and were published in the Deutsche Arzteblatt in May 24, 2002. The present study is a systematic review of the scientific literature on successful treatment in general, as well as on particular aspects of methadone substitution therapy considered by the German Medical Association's guidelines. The literature was updated until January 2004. Older randomised controlled trials and more recent quasi-experimental studies provide evidence that methadone maintenance therapy is an effective strategy to reduce illicit drug use, to improve the health situation of drug users, to diminish criminal behaviour, and to promote rehabilitation of opiate-dependent individuals. The evaluation of international studies clearly shows that access criteria to substitution therapy beyond the diagnosis of opiate dependence, e.g. the presence of a life-threatening co-morbidity, is not a prerequisite for substitution in other countries, and therefore is not discussed in the international literature. Study evidence shows that the German Medical Association's guidelines for substitution therapy of opiate dependence reflect the best evidence available from scientific studies and apply it to the conditions of the German healthcare system.