Obesity is a serious medical problem that disproportionately affects people with severe mental illness. Behavioral strategies aimed at lifestyle modification have proven effective for weight loss in general population but have not been studied adequately among persons with schizophrenia. We have conducted a randomized controlled pilot trial of an established weight loss program, modified for this specific population, and supplemented with a novel food replacement program, as well as practical, community based teaching of shopping and preparing healthy food. The program not only arrested weight gain, and produced meaningful weight loss, but also weight loss continued 6 months after the intervention is completed. Cognitive impairment had no bearing to the extent a participant benefited from the program. As a conclusion, well designed simple behavioral programs can produce lasting weight loss for patients with schizophrenia and comorbid obesity, improve metabolic indices, and possibly decrease significant medical risks associated with obesity.