This chapter reviews the differential diagnosis of combined psychosis and headache, the required evaluation, and specific treatment considerations. Patients who suffer from a primary psychotic disorder, such as schizophrenia or schizoaffective disorder, can experience headache like any other patient. Systemic lupus erythematosus is a systemic autoimmune disease that can affect virtually any part of the body, and often involves the brain. Rare metabolic disorders can also be the cause of both psychosis and headache. The treatment of patients who present with psychosis and headache must be tailored to the specific etiology. When patients suffer from a primary psychiatric disorder who suffer from somatic delusions, tactile hallucinations interpreted as headache, or those who suffer from both a psychotic disorder as well as a somatization disorder, when the appropriate psychiatric treatment is implemented to target these symptoms, both the psychosis and perceived headache should respond to treatment.