In people with schizophrenia, clinically significant psychotic symptoms can persist during treatment due to partial medication adherence, inadequate response to medication, or substance misuse. The severity of psychotic symptoms should be monitored with an assessment that is based on items from instruments such as the BPRS or PANSS. In schizophrenia, partial medication adherence is very common. Patient self-report does not provide an accurate measure of adherence. Adherence can be estimated by examining patient use of medication refills, or with biological assays of serum, 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 with consideration of potential side effects of the new medication, and by consolidating dosages, using pillboxes, or caregiver involvement and support. Cannabis, methamphetamine or other stimulant use cause psychosis, can be detected with biological assays of various matrices, including urine, and can be treated. When persistent symptoms are due to inadequate response, first, dosage can be titrated to within the therapeutic range. Second, antipsychotic medications differ in both efficacy and side-effect profiles. With inadequate response, a trial of a second antipsychotic medication is indicated, with the choice based on patient side-effect liability and efficacy. If two medication trials have resulted in inadequate improvement, clozapine should be considered. Cognitive behavioral therapy for psychosis reduces psychotic symptoms severity, though the magnitude of the change is often small, and therapy does not change the need for or use of medications.