The discovery of antipsychotic drugs for the treatment of schizophrenia has reshaped the landscape for the ability to treat this devastating disorder. However, antipsychotic drugs are not ideal, and very rarely bring the patient to the premorbid level of function. Numerous studies have shown that the presence of schizophrenia is bad for the brain, with the duration of untreated psychosis associated with a worse prognosis. Furthermore, there is evidence that the deleterious changes that take place during the premorbid phase, such as loss of inhibitory interneurons and overactivity of glutamatergic neurons, produce irreversible changes in the brain. A better approach would be to prevent the transition to psychosis in afflicted individuals. To do so, one would need to have reliable markers of susceptibility for transition to psychosis. In this series of articles, we explore biomarkers and personalized intervention strategies focused on prevention in at risk individuals. An effective approach of this type could potentially alleviate a great deal of suffering of this vulnerable population.