Eight double-blind placebo-controlled clinical trials in five countries have demonstrated the safety and efficacy of naltrexone as an adjunct in alcoholism treatment. The efficacy depends, however, on how naltrexone is used. Three of the trials tested naltrexone in two ways: (1) with supportive therapy, i.e. support of complete abstinence; (2) with therapy tacitly accepting that relapses may occur and teaching how to cope with them. Although all found benefits from naltrexone with the coping therapy, none of them found any significant benefit of naltrexone over placebo when combined with support for abstinence. These results are consistent with our pre-clinical studies in which naltrexone, naloxone, and nalmefene were effective when paired with drinking but ineffective when given during abstinence. This supported the hypothesis that the primary mechanism involved is extinction (as had been concluded earlier for the effects of naltrexone in opiate addiction treatment), because extinction only weakens responses that are made while reinforcement is blocked. On this basis, it was proposed that: (1) naltrexone should be administered to patients who were still currently drinking; (2) the instructions should be to take naltrexone only when drinking was anticipated; (3) this treatment should continue indefinitely. Subsequently, clinical trials have found that naltrexone used in this manner is safe and effective.