Multiple factors contribute to high levels of cardiovascular (CV) risk in schizophrenia patients including lifestyle habits. The additive CV effects of cigarette smoking, hypertension, total cholesterol, and high density lipoprotein (HDL) cholesterol have been found to predict the risk of major cardiac events over a 10 year period. These effects can be calculated with empirically derived CV risk algorithms. By the time the initial Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) analysis of metabolic syndrome prevalence was performed in 2005, there was already a signal that schizophrenia patients had 2-4 times higher prevalence than that expected from general population estimates. The CATIE schizophrenia trial data illustrate the possibility for improving metabolic health by switching patients from more offending medications, and for avoiding long-term CV consequences by preferential use of agents with metabolically benign profiles. Management of schizophrenia requires acknowledgment that CV disease remains a primary cause of excess mortality.