The assumption that males and females are physiologically similar has led to females being clinically evaluated and treated as males. However, there is growing evidence in the literature that, other than the reproductive system, there are other fundamental physiological differences between the two genders. The manifestation of these differences starts soon after puberty and becomes more pronounced with age. The differences in body mass and volume and renal and liver metabolism account for the difference in therapeutic efficacy and side effects of commonly used cardiovascular drugs. Women have smaller coronary arteries, more frequent diastolic dysfunction, present with vague symptoms of coronary artery disease and do worse than men after revascularization procedures. Women also have a shorter cardiac cycle and are more prone to develop arrhythmias and react differently to antiarrhythmic drugs. Most epidemiological trials that have assessed the utility of pharmacological myocardial protection or outcomes after noncardiac surgery have either been performed on men only or women were not identified as a separate group. Recent evidence is suggestive that coronary vasospasm may be the dominant etiology of acute myocardial ischemia in women. This may explain the poor sensitivity and specificity of the routine myocardial perfusion tests. Having considered all this evidence, it has become very essential to view the operative risk stratification as being gender-based. This approach may involve a shift in our present day paradigm of patient management.