Cardiovascular disease (CVD) mortality and morbidity is a major burden on the US and global population. Observed differences in prevalence, incidence, outcomes, and risk factors suggest a possible sex difference in etiology and pathophysiology of CVD. Disparate rates of referral and diagnosis may be attributable to differences in symptoms, presentation, and diagnostic accuracy. Many common procedural, pharmaceutical, and medical device therapies have been associated with worse outcomes in women compared to men. Awareness campaigns and efforts to improve female inclusion in clinical trials are contributing to improvements in CVD healthcare delivery for women, but much remains unknown about the biological basis for the differences described above, such as the role of estrogen, life-cycle changes (puberty, menstrual cycle, pregnancy, menopause), and possible chromosomal or genetic mechanisms. This is where translational research is uniquely poised to make immense contributions to resolving disparities in the quality of care and outcomes for women with CVD.