Schizophrenia is a leading cause of disability and health expenditure worldwide and is associated with homelessness, substance use, familial and social isolation, unemployment, involvement with the criminal justice system, stigma, and excess mortality. Prevention may be feasible through intervention with help-seeking "clinical high-risk" youth with early symptoms of psychosis. A social work approach to psychosis prevention would build upon initial evidence that prevention is effective for this population and would add cross-disciplinary coordination of services, mobilization of community resources, and expertise in psychosocial interventions. Recent governmental funding priorities and policies have increasingly focused on early intervention for psychosis, making rapid change feasible. This substantial potential for change, the massive savings in the quality of lives that would accrue, and the broad impact across social work domains are consistent with the goals of the American Academy of Social Work and Social Welfare's Grand Challenges Initiative.