Myocardial infarction constitutes an important health-related problem worldwide. Despite current treatments that salvage myocardial tissue and unload the left ventricle, chronic heart failure is common and is associated with increased morbidity and mortality. During the past decade, experimental studies, using cell-based therapies and growth factor administration integrated in biomaterial scaffolds, have demonstrated the potential to reduce the infarcted area and to improve regional and global left ventricular function. Some aspects of this rapid progress are reviewed in the present 'special issue' and a number of novel approaches are being introduced. This series of articles, contributed by research groups with different expertise, is a small step towards the combined efforts required to address the challenges associated with regenerating the infarcted myocardium.