LDL is oxidized in vascular endothelial cells to a highly injurious product that results in characteristic cell dysfunction(s) in large arteries and resistance vessels. The characteristic dysfunctions (ie, loss of dilation, constriction, thrombosis, and inflammation) operate before and throughout the development of atherosclerosis and particularly during plaque rupture. Although oxidized LDL appears to induce these cell/vessel wall dysfunctions in a time- and concentration-dependent manner, Tamai and colleagues have shown that this interaction can be dynamic in that a reduction in lipids restores endothelium-dependent vasomotor function almost immediately. The same intervention (ie, lipid lowering) also appears to stabilize atheroma in the long term, improves endothelium-dependent vasomotion over months, and results in a reduction in clinical signs of risk in coronary heart disease (ie, ischemia and the need for revascularization). The above leads us to some important but unanswered questions. Can we rely on clinical measures of arterial vasomotor dysfunction to represent the other important cell dysfunctions (eg, inflammation, abnormal growth) while monitoring the response to therapeutic interventions? How can we effectively inhibit oxidation of LDL in the arterial wall, and is this useful in reversing the many cell dysfunctions and clinical sequelae of coronary atherosclerosis? What is the time course for restoration of endothelial dysfunction in the atherosclerotic epicardial coronary arteries in patients with effective lipid-lowering therapy? The intracellular responses to oxidized LDL are so numerous (loss of vasodilation, loss of anticoagulant mechanisms, abnormal inflammation, and growth) that targeting therapies to specific pathways may prove difficult. Parallel efforts in basic physiological and clinical research have resulted in remarkable progress that has improved outcomes in patients with coronary heart disease. We expect that many of the characteristic cell/vessel wall dysfunctions that result from adverse interactions with risk factors are dynamic and can be manipulated in a relatively short time frame. Treatment of atherogenic lipids with other risk factors must be further refined and may well become the cornerstone for effective management of angina, unstable syndromes, and ischemia in addition to the control of important outcomes such as myocardial infarction and coronary death.