AbstractIntervention strategies in adolescents at ultra high-risk (UHR) for psychosis are promising for reducing conversion to overt illness, but have only limited impact on functional outcome. Recent studies suggest that cognition does not further decline during the UHR stage. As social and cognitive impairments typically develop before the first psychotic episode and even years before the UHR stage, prevention should also start much earlier in the groups at risk for schizophrenia and other psychiatric disorders. Early intervention strategies could aim to improve stress resilience, optimize brain maturation, and prevent or alleviate adverse environmental circumstances. These strategies should urgently be tested for efficacy: the prevalence of ~1% implies that yearly ~22 in every 100,000 people develop overt symptoms of this illness, despite the fact that for many of them—e.g., children with an affected first-degree family member or carriers of specific genetic variants—increased risk was already identifiable early in life. Our current ability to recognize several risk groups at an early age not only provides an opportunity, but also implies a clinical imperative to act. Time is pressing to investigate preventive interventions in high-risk children to mitigate or prevent the development of schizophrenia and related psychiatric disorders.