People with schizophrenia have psychotic symptoms, including disorganized thinking, hallucinations, or unreal thoughts. Significant psychotic symptoms can persist during treatment due to inconsistently taking prescribed medications, inadequate response to medication, or substance misuse. The severity of psychotic symptoms should be monitored with an assessment that is based on items from structured instruments such as the Brief Psychiatric Rating Scale. In schizophrenia, problems with medication adherence are very common. Adherence can be estimated by examining patient use of medication refills, or with assays of blood, hair or urine. Persistent symptoms due to partial adherence can be improved with the use of long-acting injectable medications, changing to a different antipsychotic medication, or by consolidating dosages, using pillboxes, or caregiver involvement and support. Cannabis, methamphetamine or other stimulant use cause psychosis, can be detected with biological assays, and can be treated. When persistent symptoms are due to inadequate response, first, dosage can be titrated to within the therapeutic range. Second, with inadequate response, a trial of a second antipsychotic medication is indicated, with the choice based on potential side-effects and effectiveness. If two medication trials have resulted in inadequate improvement, clozapine should be considered. Finally, cognitive behavioral therapy for psychosis reduces psychotic symptoms severity, though therapy does not change the need for or use of medications.