Myocardial ischemia reperfusion syndrome is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial infarction-derived damage and to heal injury. In such a setting, the establishment of an effective therapy to treat this condition has been elusive, perhaps because the experimental treatments have been conceived to block just one of the many pathogenic pathways of the disease, or because they thwart the tissue-repairing phase of the syndrome. Either way, we think that a discussion about the pathophysiology of the disease and the mechanisms of action of some drugs may shed some clarity on the topic.