In this review we discuss the sex/estrogen-specific modulation of cardiovascular function and responses to current therapeutics. We discuss how anatomical differences such as a smaller kidney size, and lower glomerular filtration rate in females, reduce the clearance and increase the toxicity of some drugs in females. Other important sex differences include the dampening effect of estrogen on central sympathetic and renin angiotensin systems. Further, we discuss how a shift in myocardial redox status leads to paradoxical transformation of estrogen into a pro-inflammatory hormone. Finally, the review, along with cited recent publications, identify some areas that need further investigation to advance our understanding of the sex differences in cardiovascular disease outcomes to help develop female specific interventions for these anomalies.