In this clinical trial, an 18-month behavioral weight-loss intervention resulted in significant weight loss in persons with serious mental illness. This vulnerable population should not be excluded from weight-loss intervention. Persons with serious mental illness, such as schizophrenia, bipolar disorder, and major depression, have mortality rates that are two to more than three times as high as the rate in the overall population, and the primary cause of death in such persons is cardiovascular disease. 1 – 4 Concomitantly, this vulnerable population has an extremely high prevalence of obesity, nearly twice that of the overall population. 5 – 9 Therefore, it is not surprising that persons with serious mental illness have an increased burden of weight-related conditions, including heightened risk of diabetes mellitus, hypertension, dyslipidemia, and certain cancers. 10 – 15 Obesity is multifactorial in persons . . .