The literature concerning the net effect of antipsychotic medication on suicidality in patients with schizophrenia is not consistent. This review assesses this problem in the light of relevant research. MEDLINE was used to search for articles written in English from 1964 to 2006. Articles were classified according to the following three orientations: positive, negative, or null effect on suicidality. Several inconsistencies among the studies and methodological difficulties appeared and a singular conclusion on this issue was not possible. Competing properties of various antipsychotic drugs may have differential effects on suicidality. Second-generation antipsychotic agents appear to have a better potential for preventing suicide in schizophrenia, but the relative profile of each drug is yet to be clarified. A good profile to treat hostility, impulsivity, and depression while not provoking extrapyramidal side effects is crucial when choosing an antipsychotic in the presence of suicide risk. The strongest and perhaps unique evidence has been shown for clozapine, which seems to have a clinically relevant advantage over both first- and second-generation antipsychotics for reducing suicidality. Although clozapine has not yet demonstrated a specific preventing effect on completed suicide in patients with schizophrenia, it should be considered when suicide risk is detected in a patient with schizophrenia.