Myocardial ischemia is considered the cornerstone of the treatment of patients with coronary artery disease (CAD). Although the deleterious effects of myocardial infarction, the maximum expression of ischemia, have been extensively studied and described, the clinical effects of chronic, documented myocardial ischemia are not completely clarified. The first studies that compared therapies for coronary disease focused on the presence of anatomical features and assessed ischemia based on the interpretation of the findings of obstructive atherosclerotic lesions. They suggested that revascularization interventions did not confer any clinical advantage over medical therapy (MT), in terms of cardiac or overall death. Other retrospective studies that were dedicated to assessing the impact of documented stress-induced ischemia on cardiovascular outcomes have suggested a prognostic impact of chronic ischemia. However, this has been questioned in recent studies. Moreover, the previous understanding that chronic ischemia could lead to worsening of ventricular function was not confirmed in a recent study. Thus, the prognostic significance of stress-induced ischemia has been questioned. Regarding treatment options, although some previous analyses have suggested that interventional therapies would reduce cardiovascular events in CAD patients with documented ischemia, recent post-hoc studies and metanalysis have shown distinct results. In this review article, the authors discuss myocardial ischemia, the different responses of the myocardium to ischemic insults, ischemic preconditioning, and the main findings of recent studies about the clinical aspects and treatment of patients with chronic, documented myocardial ischemia.