Substance use disorders are prevalent co-occurring problems among people with schizophrenia, with lifetime rates approaching 80% in this population when tobacco use is taken into account. Substance use disorders are associated with significant adverse effects among people with schizophrenia, including worse psychiatric symptoms, lower functioning, and increased medical morbidity and mortality compared with schizophrenia patients without co-occurring substance use. The etiology of this relationship is multifactorial, involving neurobiological, genetic, and environmental factors. The substances most commonly used by people with schizophrenia are tobacco, alcohol, cannabis, and cocaine. Screening, diagnosis, and treatment of substance use disorders are important and can have significant effects on clinical outcomes. Treatments for comorbid disorders include psychopharmacological, psychotherapeutic, and multidisciplinary interventions. Several medications have been approved by the U.S. Food and Drug Administration for the treatment of substance use disorders, which also appear to be helpful for patients with schizophrenia, although few controlled trials have been conducted specifically in this population. Psychosocial and psychological interventions have been adapted for use among patients with schizophrenia as well. Treatment of both psychotic illness and substance use disorders in an integrated way improves functional and clinical outcomes.