We report the use of naltrexone for treatment of alcohol use disorder in patients with major psychiatric illness. We reviewed the records of 72 mentally ill outpatients treated with naltrexone for alcohol use disorders at a community mental health center. The psychiatric diagnoses included major depression (n = 37), schizophrenia (n = 17), bipolar illness (n = 11), schizoaffective disorder (n = 7), and gender identity disorder (n = 4). Sixty-one patients (85%) had histories of psychiatric hospitalization. Total retention in naltrexone treatment for at least eight weeks was 81.9%: 5 (6.9%) were lost to follow-up, and 8 (11.1%) discontinued the medication because of side effects, primarily nausea. Patients showed good clinical response to naltrexone, with 82% reducing their drinking by at least 75%, and only 17% relapsing at eight weeks. We conclude that naltrexone is useful in the treatment of dually-disordered patients. The hypothesis that clinical response to naltrexone is facilitated by active alcohol drinking during treatment is discussed.