Purpose. The effectiveness and tolerability of switching patients' therapy from brandname to generic clozapine are reviewed. Summary. Clozapine is the most effective treatment for patients with refractory psychotic disorders and is also effective for reducing suicidal and violent behavior in this same population. Generic versions of clozapine are widely used. However, possible differences in pharmacokinetic profiles between branded and generic clozapine, and the potential risks of medication changes in severely ill but stable patients, may result in apprehension about converting from branded to generic clozapine. Articles, abstracts, and clinical presentations that compared clinical outcomes between Clozaril (Novartis Pharmaceuticals, East Hanover, NJ) and generic forms of clozapine in patients with primary psychotic disorders, bipolar disorder, or related conditions were identified via a computerized search of the medical literature. Thirteen relevant reports, mostly uncontrolled observational studies or chart reviews, described the effects of switching from brand-name to generic clozapine in 966 patients. The majority of patients tolerated conversion without worsening of symptoms or adverse effects, increased intensive service utilization, or medication adjustment. Clinical deterioration was described in a case review and in one randomized, controlled study. Conclusion. Available literature supports the effectiveness and safety of generic clozapine formulations in patients who previously were stable during treatment with brand-name clozapine. The risk of poor outcome after conversion to a generic clozapine formulation appears to be low but difficult to predict. Patients should be closely monitored during the first one to three months after conversion from one formulation to another. Copyright © 2010, American Society of Health-System Pharmacists, Inc. All rights reserved.