Clozapine is a great advance in the treatment of schizophrenia. It should be tried in any neuroleptic-resistant schizophrenic as well as some who are neuroleptic intolerant. If progress is made in controlling its agranulocytosis, clozapine could be the drug of choice for all types of schizophrenia and perhaps other conditions as well for which neuroleptic drugs are employed, e.g., mania resistant to mood stabilizers. Its advantage with regard to lower risk of tardive dyskinesia indicates that potent antipsychotic activity and liability to cause tardive dyskinesia can be dissociated. This must be the object of future antipsychotic drug development. Risperidone could be the next clozapine but at the time of this writing, there is too little data to pass judgment on this. Its low EPS profile and apparent effects on negative symptoms at lower doses are promising. Remoxipride may be useful because of its low EPS profile. How much better tolerated it is than currently available drugs, especially thioridazine, is not clear. Many other novel agents are being tested. Clinicians will be challenged to follow this emerging field closely and identify the most promising new agents that may be indicated for specific stages of, or subtypes of, schizophrenia.