Recent research shows that in first episode schizophrenia the chance of response to an antipsychotic trial decreases from 75% in the first trial to 17% in the second. A subsequent trial with clozapine has a response rate of 75% again. Studies show a significant higher response rate at clozapine plasma trough levels above a therapeutic threshold of 350–400 ng/ml. The absolute risk difference is about 40%. In children and adolescents with therapy-resistant early onset schizophrenia spectrum disorder clozapine appears to be superior to olanzapine and haloperidol. Clozapine has a superior effect on aggression in patients with psychotic disorders. Case series point to an anti-aggressive effect in non-psychotic disorders too. Comparison of patients on clozapine to patients on other antipsychotics shows decreased rates of suicide and suicide attempts. A randomised controlled trial in patients with schizophrenia or schizoaffective disorder and a high risk for suicidality shows an absolute risk difference of 2,9% of suicide attempts per year in the clozapine group versus the olanzapine group. In observational studies more patients on clozapine get into remission and maintain remission of alcohol and substance abuse or dependance than on other antipsychotics. Thus clozapine has a place beyond therapy resistance in schizophrenic patients with aggression, suicidality or alcohol and substance abuse/dependance.