"Recently, it has been shown that the heart can be protected against the ischemia-reperfusion injury if brief coronary occlusions are performed just at the beginning of the reperfusion. This procedure has been called postconditioning (PostC). It can also be elicited by pharmacological interventions, which are named pharmacological PostC. In general, PostC reduces the reperfusion- induced injury, blunts oxidant-mediated damages and attenuates the local inflammatory response to reperfusion, decreases infarct size, diminishes apoptosis, neutrophil activation, and endothelial dysfunction. The mechanisms that participate in PostC are still not completely understood. In this regard, adenosine, glycine, bradykinin, ciclosporin A are involved in PostC triggering. Similar to ischemic preconditioning, PostC triggers several signaling pathways and molecular components, including nitric oxide (NO), protein kinase C, adenosine triphosphate-sensitive potassium channels, the Reperfusion Injury Salvage Kinases (RISK) pathway, which comprises phosphatidylinositol-3-OH kinase (PI3K) and extracellular signal-regulated kinase (ERK 1/2), and, finally, the Survivor Activating Factor Enhancement (SAFE) pathway. In this review, we describe the mechanisms of reperfusion-induced injury as well as the proposed protective pathways activated by PostC, which seem to converge in inhibition of mitochondrial permeability transition pores opening. On the other hand, experimental evidence indicates that volatile anesthetics and opioids are capable of exerting cardioprotective effects under certain conditions, constituting a very useful pharmacological PostC. Thus, the first minutes of reperfusion represent a window of opportunity for triggering the aforementioned mediators, which acting in concert lead to protection of the myocardium against reperfusion injury. Pharmacological, especially anesthetic, PostC may have a promising future in the clinical scenarios in the operating room."