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Since publication of the original Schizophrenia Patient Outcomes Research Team (PORT) treatment recommendations in 1998, considerable scientific advances have occurred in our knowledge about how to help persons with schizophrenia. Today an even stronger body of research supports the scientific basis of treatment. This evidence, taken in its entirety, points to the value of treatment approaches combining medications with psychosocial treatments, including psychological interventions, family interventions, supported employment, assertive community treatment, and skills training. The most significant advances lie in the increased options for pharmacotherapy, with the introduction of second generation antipsychotic medications, and greater confidence and specificity in the application of psychosocial interventions. Currently available treatment technologies, when appropriately applied and accessible, should provide most patients with significant relief from psychotic symptoms and improved opportunities to lead more fulfilling lives in the community. Nonetheless, major challenges remain, including the need for (1) better knowledge about the underlying etiologies of the neurocognitive impairments and deficit symptoms that account for much of the disability still associated with schizophrenia; (2) treatments that more directly address functional impairments and that promote recovery; and (3) approaches that facilitate access to scientifically based treatments for patients, the vast majority of whom currently do not have such access.