It is known that early treatment improves the outcome in patients with schizophrenia. Treatment interventions prior to the onset of frank psychosis hold the promise of even better outcomes. Since schizophrenia typically has a year long prodromal phase before becoming clinically manifest, the field has made increasing efforts to define reliable criteria for subjects who are at high risk for psychosis (at-risk mental state, ARMS subjects). Still, no single test exists that would be sensitive and specific enough to justify individual treatment decisions in ARMS subjects. The most prominent theory on the pathogenesis of schizophrenia, the dopamine hypothesis, has undergone several modifications since its formulation more than half a century ago. Although there is nearly indisputable evidence for increased dopamine neurotransmission in schizophrenia, recent theories suggest that increased dopamine function is not causal, but can be seen as a final common pathway mediating psychosis in schizophrenia. Dopaminergic and glutamatergic neurons interact at striatal interneurons to control striatal output and information processing in fast glutamatergic networks. Both, glutamatergic and dopaminergic neurotransmission, are believed to be already altered in prodromal phases of schizophrenia.. Results from neuroimaging studies indicate that dopamine transmission is altered before the outbreak of psychosis, and recent findings also suggest alterations in dopamineglutamate coupling in ARMS subjects. Improved methods for imaging dopamine and glutamate function in the living brain have thus the potential to identify young people at ultra- high risk who would most likely benefit from early psychological and pharmacological interventions.