The notion that cardiovascular disease (CVD) primarily occurs in men is slowly disappearing. More women than men die of CVD every year, and when women survive, the burden and consequences are worse than in men. Markers of stress and other psychosocial factors have been associated with poor outcomes. Multiple studies have demonstrated sex-based differences in the vascular and endothelial responses to mental stress. Psychosocial stressors were also found to be independent risk factors for the development and progression of CVD. This review arises from accumulating evidence suggesting that psychological well-being may improve cardiac-related outcomes, independent of cardiac risk factors. Despite the fact that positive physician-patient engagement is likely to play a critical role in promoting positive psychological traits and healthy behaviors, current physician awareness and advocacy are rather suboptimal, despite active awareness campaigns such as the American Heart Association’s Go Red for Women®. There is a need to further study the role and management of stress as a CVD risk factor, especially in women, who are disproportionately affected.