A significant minority of patients with schizophrenia fail to respond to neuroleptic medication alone. In some of these patients, adjunctive treatment with benzodiazepines may prove beneficial. Preclinical studies suggest that benzodiazepines significantly decrease brain dopamine release and turnover, perhaps by augmenting gamma-aminobutyric acid (GABA) inhibition of dopamine neuron activity. Double-blind clinical studies, however, have not conclusively established a role for benzodiazepines in the treatment of schizophrenia, and it seems likely that some patients respond favorably, whereas others do not. We review preliminary new observations that approximately half of a group of treatment-resistant patients, studied in a double-blind treatment protocol, demonstrated clinically significant antipsychotic responses to adjunctive alprazolam. We also briefly describe long-term efficacy of alprazolam in several patients whom we have followed in open-label clinical settings. Possible predictors or biological concomitants of benzodiazepine responsivity, which may aid in delineating distinct subgroups of patients, are discussed, and recommendations for future research are presented.