In schizophrenia, once psychosis and negative symptoms have manifested, most patients will suffer from persistent illness and declining social and vocational functioning; hence prevention has been contemplated for many years (1). In the early 1990s, the perception that second-generation antipsychotics improved the risk-benefit ratio of antipsychotic treatment was the impetus for investigators to attempt to diagnose and treat the illness before the appearance of full-blown psychosis. It was hypothesized that early intervention, including supportive therapy and treatment with antipsychotics, might prevent or delay the first psychotic episode and the subsequent deterioration (2). In order to identify these future patients, diagnostic criteria for this prodromal phase of the illness were developed and agreed upon, based on the presence of attenuated or brief positive symptoms or decreased functioning in persons with a first-degree relative with schizophrenia. Initial results indicated that 40% of patients who met these criteria transitioned to full-blown psychosis within a year (3). Specialty clinics were established, professional organizations were formed to promote investigation in this field, and new assessment tools were developed to quantify prodromal symptoms. The National Institute of Mental Health funded the North American Prodromal Longitudinal Study, in which the leading prodromal researchers in the United States and Canada pooled their data to further the study of the prodromal phase. Impressive prediction models were published in prestigious journals, positive treatment trials encouraged the use of second-generation antipsychotics in these patients (4, 5), and more and more clinicians began to administer antipsychotics to patients with attenuated psychotic symptoms (6). However, as time went on, the rates of transition from prodrome to psychosis dropped below a range of 15%—20% (7, 8). There are several possible explanations for the decline. Publicity and increased awareness led to earlier referrals, and hence patients were assessed earlier in the period of risk, leading to the recruitment of a more dilute sample, including more false positives. In addition, increased exposure of putative prodromal patients to pharmacological and psychosocial interventions might result in fewer transitions to psychosis (9). Around the same time, it became clear that the second-generation antipsychotics were marginally if at all more efficacious than the old drugs and had significant metabolic side effects, which led to a reshifting of the risk-benefit ratio (10).