The drugs most diverted for toxicomanic use from their therapeutic indication are principally the opioids or related substances, with codeine still high in importance, in spite of the wide prescription of substitution treatments. The psychotropic drugs, essentially the benzodiazepines and the stimulant antidepressants such as amineptine, are also frequently used. The market withdrawal of amineptine should diminish its misuse. The abuse of amphetamines-anorectics and barbiturates seems to be regressing. Nevertheless, substances such as nitrous oxide and ketamine are the subject of selective, recent misuse. Moreover high-dose buprenorphine misuse, as a concomitant buprenorphine-benzodiazepine combination and/or an intravenous injection of high doses of buprenorphine, can be implicated in severe adverse effects. Twenty-one lethal intoxications linked to such drug misuse have already been reported. However, the addictive drug potential is not the only explanation for drugs diverted for toxicomanic use. It is also associated with a polytoxicomania, a symptom of pre-existing difficulties, particularly familial, social and environmental in origin. Therefore, the therapeutic regime should be adapted to the drug addict's personality. We report a few cases of polydrug abusers, treated with methadone in a specialist unit. The misuse and the practical therapeutic response, adapted to each case, are compared and discussed in respect of the data published in the literature.