Recent improvements in the clinical management of acute myocardial infarction (MI) have resulted in a dramatic decrease in mortality because of this condition. This implies that more patients enter the process of infarct healing. This is a highly complex cascade of events which, although studied for decades, is still not completely understood. An increasing number of genetically altered mice can now be studied in a mouse model of MI, to investigate the contribution of the product of the targeted gene to the infarct healing process. In this review, we will discuss the defects in infarct healing that have been observed in null mutants for plasminogen, urokinase-type plasminogen activator (u-PA), matrix metalloproteinases (MMPS), thrombospondin-2 and dishevelled-1. These studies provide new insights in the infarct healing process itself, but may also help to define new diagnostic and therapeutic targets in humans suffering from MI.