During the last 10 years new approaches for rapid opioid detoxification have included drug combinations such as clonidine and naltrexone to speed and ease the transition from opioid agonist to antagonist maintenance. Other drug combinations include naloxone with midazolam or methohexitone for inpatients, but rapid outpatient methods are more desirable. Clonidine combined with naltrexone enables abrupt opioid withdrawal in 3–5 days in an outpatient/day setting. This approach can be further improved by transition to the partial agonist buprenorphine from either heroin or methadone followed by a 1 day detoxification using naltrexone precipitated withdrawal, ameliorated by clonidine.