As the prevalence of obesity continues to grow worldwide, the health and financial burden of obesity-related comorbidities grows too. Cardiovascular disease (CVD) is clearly associated with increased adiposity. Importantly, women are at higher risk of CVD when obese and insulin resistant, in particular at higher risk of developing heart failure with preserved ejection fraction and ischemic heart disease. Increased aldosterone and mineralocorticoid receptor activation, aberrant estrogenic signaling and elevated levels of androgens are among some of the proposed mechanisms explaining the heightened CVD risk. In addition to traditional cardiovascular risk factors, understanding nontraditional risk factors specific to women, like excess weight gain during pregnancy, preeclampsia, gestational diabetes, and menopause are central to designing personalized interventions aimed to curb the epidemic of CVD. In the present review, we examine the available evidence supporting a differential cardiovascular impact of increased adiposity in women compared with men and the proposed pathophysiological mechanisms behind these differences. We also discuss women-specific cardiovascular risk factors associated with obesity and insulin resistance.