Antipsychotic medication can substantially improve acute psychotic symptoms, however, there is an increasing concern about long-term effects of anti-psychotic medication. We review brain imaging studies that assess prefrontal cortical volume in longitudinal designs and report the effects of neuroleptic dose as well as symptom severity. In these prospective studies, a majority of studies reported a significant effect of neuroleptic dose on brain volume reductions when controlling for symptom severity. These findings strengthen the concern that long-term and rather high dose neuroleptic medication contribute to prefrontal cortical atrophy. Low doses and psychosocial and psychotherapeutic interventions that help to reduce the need for medication therefore are highly warranted.