All volatile anesthetics have cardiac depressant effects that decrease myocardial oxygen demand and may thus improve the myocardial oxygen balance during ischemia. Recent experimental evidence has clearly demonstrated that, in addition to these indirect effects, volatile anesthetic agents also directly protect from ischemic myocardial damage. Implementation of these effects during clinical anesthesia can provide an additional tool for treatment or prevention of ischemic cardiac dysfunction during the perioperative period. A recent meta-analysis showed that desflurane and sevoflurane reduce postoperative mortality and the incidence of myocardial infarction following cardiac surgery, with significant advantages in terms of postoperative cardiac troponin release, need for inotropic support, and time on mechanical ventilation, as well as in time spent in the intensive care unit and overall hospital stay. Multicenter, randomized clinical trials previously demonstrated that desflurane could reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft surgery, either with or without cardiopulmonary bypass. However, evidence in non-coronary surgical settings is contradictory and will be reviewed in this paper, together with the mechanism of cardiac protection by volatile agents.