Between 4 and 13% of people with schizophrenia commit suicide and between 25 and 50% make a suicide attempt, a reflection of the devastating toll this syndrome takes on the quality of life, that is, the subjective and objective sense of well-being. Many risk factors for suicide in schizophrenia have been identified, the most important of which are previous suicide attempts, depression, hopelessness, substance abuse, and male gender. Insight into having a serious mental illness and less severe cognitive impairment are also associated with increased risk for suicide in schizophrenia, most likely when accompanied by feelings of hopelessness. Typical neuroleptic drugs have not been shown to reduce the risk of suicide. However, several types of evidence suggest that clozapine, an atypical antipsychotic drug, appreciably reduces the suicide attempt and completion rates in schizophrenia and schizoaffective disorder, perhaps by as much as 75-85%. Other atypical antipsychotic drugs may have a similar effect, but direct evidence is lacking. Improvement in positive and negative symptoms, reduced extrapyramidal side effects (EPS), a direct antidepressant action, improved cognitive function, and improved compliance may contribute to reduced suicidality. The International Suicide Prevention Trial (InterSePT) is a large prospective, randomized study intended to compare the effectiveness of clozapine with that of olanzapine in reducing suicide and suicide-related events in schizophrenic and schizoaffective patients. Some information about suicidality in the patient sample is reported here.