Cardiovascular disease (CVD) has been the primary cause of death in women for almost a century, and more women than men have died of CVD every year since 1984. Although CVD incidence can be reduced by adherence to a heart-healthy lifestyle and detection and treatment of major risk factors, preventive recommendations have not been consistently or optimally applied to women. The American Heart Association guidelines for CVD prevention in women provide physicians with a clear plan for assessment and treatment of CVD risk and personalization of treatment recommendations. The emphasis of preventive efforts has shifted away from treatment of individual CVD risk factors in isolation toward assessment of a woman's overall or "global" CVD risk. In addition to accounting for the presence or absence of preexisting coronary heart disease or its equivalents (e.g., diabetes, chronic kidney disease), cardiovascular risk can be further calculated with the Framingham risk score, which is based on age, sex, smoking history, and lipid and blood pressure levels. Intervention intensity and treatment goals are tailored to overall risk, with those at highest risk receiving the most intense risk-lowering interventions. Women at high risk for CVD and without contraindications should receive aspirin, beta blockers, and an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in addition to pharmacologic therapy for hyperlipidemia, hypertension, and diabetes. Women who already are at optimal or low risk for CVD should be encouraged to maintain or further improve their healthy lifestyle practices. Optimal application of these preventive practices significantly reduces the burden of death and disability caused by heart attack and stroke in women.