Brain imaging studies with PET, SPECT, functional magnetic resonance imaging, and spectroscopy provide evidence of prefrontal dysfunction in schizophrenia. Dysfunction of the prefrontal cortex is associated with cognitive impairment and negative symptoms. Combined multimodal imaging shows that a developmentally early disturbance of frontotemporal-limbic neuronal networks is associated with a disinhibition of subcortical dopaminergic neurotransmission. Current studies imply genetic factors in the regulation of dopaminergic neurotransmission and their effects on prefrontal cortex function. Some studies also indicate that atypical neuroleptics may at least partially improve frontal cortex function. We review the literature and discuss genotype and medication effects on frontal dysfunction in schizophrenia. Molecular brain imaging combines imaging techniques with the assessment of genotype effects and represents a powerful tool for the understanding of neuropsychiatric disorders.