Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality for women in the United States and worldwide. There has been no American College of Cardiology (ACC)/American Heart Association guideline update specifically for the prevention of CVD in women since 2011. Since then, the body of sex-specific data has grown, in addition to updated hypertension, cholesterol, diabetes, atrial fibrillation, and primary prevention guidelines. The ACC CVD in Women Committee undertook a review of the recent guidelines and major studies to summarize recommendations pertinent to women. In this update, the authors address special topics, particularly the risk factors and treatments that have led to some controversies and confusion. Specifically, sex-related risk factors, hypertension, diabetes, hyperlipidemia, anticoagulation for atrial fibrillation, use of aspirin, perimenopausal hormone therapy, and psychosocial issues are highlighted.