Patients with schizophrenia have increased rates of morbidity and mortality due primarily to cardiovascular disease, compared with the general population. Case reports, case series, observational analytic epidemiologic studies, and randomized trials raise the possibility that some antipsychotic drugs add to this increased risk, likely due to drug-induced weight gain and associated metabolic abnormalities including hyperglycemia, diabetes mellitus, and dyslipidemia. This constellation of risk factors, referred to as the "metabolic syndrome" leads to greater than additive risks and affects about 1 in 4 adult Americans, approximately 60% of obese adults,1,2 and perhaps 1 in 2 patients with schizophrenia. At the time of initiating treatment in their patients with schizophrenia, psychiatrists should be aware of metabolic and cardiovascular risk factors, as well as subsequent treatment-induced changes in risk status. Awareness of established risk factors for major morbidity and mortality should influence choice of antipsychotic medications, based on differences in the potential effect of individual medications on weight and related metabolic and cardiovascular risk. Strategies recommended include identifying high-risk patients, promoting healthy lifestyle/behavioral habits, selecting antipsychotic medication regimens with comparable efficacy and fewer metabolic side effects, and monitoring weight, glucose, and lipid profiles during treatment.