Idazoxan, a potent alpha 2 antagonist, has been used in patients with schizophrenia who are currently treated with the typical neuroleptic, fluphenazine. This approach is based on evidence that the therapeutically superior, atypical neuroleptic, clozapine, is a relatively potent antagonist of alpha2 receptors. Preliminary data suggest that the combination of idazoxan with fluphenazine improves total, positive and negative symptoms in schizophrenia. Correlations between symptom improvement and biochemical measures suggest that enhancement of noradrenergic neurotransmission by idazoxan underlies its clinical effects. Continued research investigating the clinical use of idazoxan and the biochemical mechanisms underlying its effects may lead to improved augmentation of neuroleptic treatment and innovations in drug development for schizophrenia.