Even after the introduction of the new atypical antipsychotics clozapine as yet has an unequalled superior efficacy in refractory schizophrenia. Unfortunately, it has also some rare but dangerous side-effects. Nevertheless, the overall mortality in patients with schizophrenia decreases with treatment with clozapine. Patients who have been treated with a classical and a new atypical antipsychotic with only partial or no response should be offered a trial with clozapine.