Myocardial infarction due to coronary heart disease is the major cause of death in developed countries and a major determinant for the development of heart failure. Within the last 30 years there has been intense research into cardioprotective therapies capable of limiting cardiac damage due to infarction. However, despite a better comprehension of the molecular and cellular mechanisms triggered during the ischemic insult and further revascularization, and encouraging experimental studies and proof-of-concept clinical trials, very few of the tested agents/interventions have translated to successful clinical trials and none is on standard clinical use. The failure in translation of cardioprotection to clinical practice has been attributed to many factors, from inadequate animal models to poor clinical study designs. In addition, patients usually have cardiovascular risk factors, co-morbidities and concomitant medications that cannot be overlooked since they may interact with the cardioprotective response. Besides improving the design of the experimental and clinical studies the search for new cardioprotective agents must continue. The use of emerging “omic” technologies and bioinformatics tools holds great promise to identify novel targets of therapeutic relevance and new treatment approaches able to limit the damage of myocardial infarction and attenuate the consequent adverse left ventricular remodeling process.