Clozapine (Clozaril) has been available in the United States for about 20 years for use with patients who have treatment-resistant schizophrenia or patients who are unable to tolerate the side effects of first-generation antipsychotics. Clozapine was in many ways the best new development in the treatment of schizophrenia since chlorpromazine was discovered. The drug does have problems and dangers, it does not work for everyone, and patients who are helped substantially may still be far from well. However, it is thus far the only antipsychotic drug that has been shown in controlled studies to be clearly more effective than older antipsychotics in resistant schizophrenia. It is also thus far the only antipsychotic drug that causes essentially no pseudoparkinsonism or dystonia and that is, apparently, unlikely to cause tardive dyskinesia.