Naltrexone is an opiate antagonist used as a pharmacologic adjuvant for the treatment of opiate and alcohol addiction. It has been hypothesized that naltrexone blocks the stress-response and well-being effects associated with opioid peptides. This raises the clinical concern that naltrexone may cause dysphoria. The authors reviewed pharmacological and clinical data in alcohol, opioid, and nicotine studies to determine if an association between naltrexone and dysphoria exists. These studies did not reveal dysphoria to be a serious side effect produced by naltrexone treatment. Additional studies to evaluate long-term endocrine effects and antidepressant combination therapy are warranted.