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confirmed in subsequent trials and has changed our understanding of the mechanisms underlying antipsychotic treatment.Previous attempts to develop new antipsychotic drugs had been influenced by the dopamine hypothesis, supported by the observation that all effective antipsychotic drugs exhibited some degree of D2 dopamine receptor antagonism.9The fact that clozapine is only a weak D2 blocker suggests that mechanisms other than D2 blockade must be relevant for the control of positive symptoms.We do not know which of the neurotransmitter mechanisms affected by clozapine (dopamine receptor subtypes, serotonin, or a adrenergic effects) is responsible for its benefits in patients who are resistant to treatment.Another drug with evidence of enhanced effectiveness, risperidone, has D2 and 5HT2 receptor blocking properties.10Clarifying the mode of action of more effective drugs is likely to provide a key to understanding treatment resistance. Imaging links symptoms and brain functionOther approaches are also bearing fruit.Functional imaging techniques have considerable potential for examining the relations between psychotic symptoms, performance in neuropsychological tests, response to drug treatment, and blood flow in different regions of the brain.Positron emission tomography has shown that different symptom patterns in patients with schizophrenia produce different patterns of cerebral blood flow."Functional magnetic resonance imaging, which does not involve ionising radiation and permits multiple repeat examinations, may clarify the relation between symptom patterns, drug effects, and regional brain fimction.Such work may allow the considerable theoretical advances that have occurred in schizophrenia research over the past 20 years to start to be translated into therapeutic benefit for current sufferers.