Compared with the general population, persons with schizophrenia have up to a 20% shorter lifespan, with cardiovascular disease as the leading cause of death. In addition, persons with schizophrenia have increased prevalence of the metabolic syndrome (obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, and hypertension), increased prevalence of risk factors such as smoking, poverty, and poor nutrition, and reduced access to medical care. Results from the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) provide further evidence of the metabolic risk associated with different atypical antipsychotics. Based on this study and a growing number of other randomized clinical trials, clozapine and olanzapine treatment can produce substantial mean changes in weight and an increased risk of associated metabolic disturbances. Risperidone and quetiapine treatment can produce intermediate changes in mean weight in comparison to treatment with other atypical antipsychotics, with discrepant results with respect to metabolic risk. Aripiprazole and ziprasidone treatment induced the lowest mean changes in weight gain and had no effect on risk for adverse metabolic changes, among currently available atypical agents. Considerable evidence indicates that mentally ill patients often do not receive adequate recognition of, monitoring of, or care for their medical illnesses. There is a critical need for psychiatrists and primary care professionals to increase awareness of and attention to the physical health problems of persons with mental illness, including appropriate management of metabolic adverse events associated with psychiatric medications.