Wounding and healing are archaic principles, prerequisite for survival of any biologic material. However, strategies to cope with wounding may be quite different among organisms, species, or among various organs of one species. Today, myocardial infarction and the consequent loss of fully functional myocardium is the major aetiology for heart failure. Despite aggressive primary therapy, prognosis remains serious in patients with large infarction and severe left ventricular dysfunction. Thus, it would be highly desirable to influence healing of the cardiac wound to maintain structure and function of the heart. Herein, we review different, important factors of cardiac healing including reperfusion, mechanical stress, gender, and neurohormonal factors as well as specific factors essential for healing which may be genetic or acquired, emphasizing similarities and discrepancies between different organs and species.