Recent progress in understanding the pathophysiology of myocardial ischemia provides a more complex causal pathway than the heretofore notion of fixed atherosclerotic obstructions in passive conduits. Diseased arteries which may appear angiographically normal as well as arteries with fixed obstructions can respond to vasomotor influences with a detrimental amount of vasoconstriction. The endothelium generates vasoactive and anticoagulant factors that are important mediators of thrombosis. Cycling hormones may further influence these complex interactions. Methods which do not rely solely on fixed obstruction of epicardial arteries are not only possible but may be useful to recognize early atherosclerosis or, for example, endothelial dysfunction which places the patient at risk for untoward coronary events.