In patients with coronary artery disease, angina pectoris provides an unreliable underestimation of disease activity and risk. Unheralded myocardial infarction and sudden death are common clinical presentations. Furthermore, objective testing, in hospital and more recently during the patient's normal daily activities, has demonstrated frequent and asymptomatic episodes of ischemia, as indicated by transient ST-segment depression. Since the underlying pathophysiologic disturbances of myocardial perfusion appear to be similar in painful and painless episodes, it seems appropriate to consider them together as the "total ischemic burden" on the myocardium. Research into this functional expression of coronary disease has indicated that active ischemia is associated with an increased risk of morbid events in all clinical subgroups of patients, including those with stable angina, unstable angina, peripheral vascular disease and following myocardial infarction. If this is confirmed in prospective trials, the assessment of total ischemic burden is likely to become part of the clinical investigation of patients with coronary disease. Clinical trials testing the efficacy of interventions will need to examine the effect on ischemic activity during normal daily life, in addition to symptoms and exercise tolerance. Evidence is still required to demonstrate whether therapy aimed at reducing the total ischemic burden will prolong life. The total ischemic burden provides a marker to follow the dynamic changes of the atherosclerotic lesion. Future research may have to concentrate on treatment aimed at altering the natural history of obstructive coronary atherosclerosis in order to affect the long-term outlook for patients with coronary artery disease.