During major vascular surgery (MVS), patients are at high risk for developing unrecognized myocardial infarction (MI) and myocardial ischemia. In reducing postoperative morbidity and mortality, preoperative cardiac risk stratification and adequate medical therapy play a pivotal role. Based on literature and current opinions, medical treatment should comprise at least a combination of beta-blockers, aspirin, and statins. beta-Blockers exert their beneficial effects predominantly through heart rate control, leading to reduced oxygen demand during surgery. A heart rate between 65 and 70 bpm should be achieved. Irrespective of their lipid-lowering effects, statins seem to improve postoperative cardiac outcome by stabilizing coronary artery plaques, thereby preventing atherosclerotic plaque rupture. Aspirin reduces platelet activation and vasoconstriction, thereby limiting ischemic events and reducing nonfatal MI by 34%. Adding clopidogrel to low-dose aspirin might be beneficial toward postoperative cardiac outcomes; however, the effect on the incidence of postoperative bleeding complications may be a problem for future studies to resolve. Whereas beta-blockers inhibit the effect of catecholamines, alpha(2)-agonists inhibit catecholamine release and may be used in the perioperative setting when beta-blockers are contraindicated. Despite the blood pressure-lowering effect and anti-inflammatory properties of angiotensin-converting enzyme inhibitors, the literature does not support their use in patients undergoing MVS. The possible use of calcium antagonists before MVS should be further evaluated in high-risk patients with contraindications to beta-blockers, such as asthma, conduction abnormalities, or a history of stroke. Although nitrates are widely used for treating angina pectoris, the beneficial effect of their use in patients undergoing MVS remains controversial. Therefore, nitrates are not routinely used in the perioperative setting. The current American College of Cardiology/American Heart Association guidelines do not recommend prophylactic coronary revascularization before noncardiac surgery in patients with stable coronary artery disease.