Silent myocardial ischemia is a relatively common, but poorly understood, clinical entity. The most accurate means of detecting silent myocardial ischemia and the precise treatment endpoints remain unclear. However, the amount of ischemic myocardium appears to correlate with the likelihood of future adverse cardiac events. Evidence suggests that patients at highest risk of severe myocardial ischemia, even in the absence of symptoms, derive the greatest benefit from an aggressive diagnostic and therapeutic approach. This paper reviews the diagnosis and treatment of silent myocardial ischemia, and its clinical implication in select patient groups: those without coronary artery disease, those with coronary artery disease, diabetic patients, postrevascularization patients, and women.