In this article, the authors reevaluate the traditional position that benzodiazepines should be avoided in anxiety disorder patients with a history of substance abuse or dependence. The efficacy of benzodiazepines in each of the anxiety disorders is reviewed, as are their side effects and toxicity. The definitions of benzodiazepine abuse and dependence are discussed, and relevant animal, experimental, and clinical data are reviewed and analyzed. A manual and computerized (MEDLINE) search was performed from 1966 to the present to examine the English-language literature published on benzodiazepines, substance abuse, and each of the anxiety disorders listed in DSM-IV. The authors found that benzodiazepines have demonstrated efficacy in generalized anxiety disorder, panic disorder, and agoraphobia; they are promising agents in the treatment of social phobia and alcohol-induced anxiety disorders. They are generally well tolerated. There is much ambiguity over appropriate definitions for benzodiazepine abuse and dependence: although most benzodiazepine abusers concurrently abuse other substances, there is little evidence to indicate that a history of substance abuse is a major risk factor for future benzodiazepine abuse or dependence. Furthermore, benzodiazepines do not appear to induce relapse of substance abuse in these patients. The authors conclude that the position that benzodiazepines are contraindicated in former substance abusers appears to lack empirical justification. Benzodiazepines may be indicated in certain patients with anxiety disorders and a history of substance abuse or dependence. (Am J Addict 2001;10:48-68)