Cardiovascular disease (CVD), which includes coronary heart, cerebrovascular, and peripheral vascular disease, is the leading cause of death in the United States and most developed countries, accounting for about 50% of all deaths. The major risk factors include obesity and its consequences, dyslipidemia, hypertension, insulin resistance leading to diabetes, and cigarette smoking. In developing countries, CVD will become the leading cause of death due to alarming increases in obesity, sedentary lifestyles, cigarette smoking, and improvements in prevention and treatment of malnutrition and infection. Compared with nonschizophrenics, patients with schizophrenia have a 20% shorter life expectancy (i.e., from 76 to 61 years). In general populations, about 1% die from suicide compared with about 10% among patients with schizophrenia (relative risk = 10). For CVD, the corresponding figures are 50% and about 75% (relative risk = 1.5). In patients with schizophrenia, however, CVD occurs more frequently and accounts for more premature deaths than suicide. Patients with schizophrenia have alarmingly higher rates of obesity, dyslipidemia, hypertension, diabetes, and cigarette smoking than nonschizophrenic individuals in the general population. Compounding these data, patients with schizophrenia have less access to medical care, consume less medical care, and are less compliant. Primary prevention strategies should include the choice of antipsychotic drug regimens that do not adversely affect the major risk factors for CVD.