Primary percutaneous coronary intervention (PCI) is currently recognized as a highly effective therapy for acute myocardial infarction (AMI) and has been shown to decrease myocardial damage and improve prognosis. Several diagnostic tools have been proposed to evaluate the myocardium at risk, the occurrence of no-reflow, the final scar size, and the presence of residual viable myocardium in patients treated by primary PCI. A large body of literature documents the relevant impact of each of these variables on outcomes in patients treated for AMI. In patients undergoing primary PCI, a number of treatment approaches have been proposed recently to improve efficacy by increasing myocardial salvage. This article describes the principal diagnostic tools (ie, serum biochemical markers, electrocardiography, echocardiography, nuclear imaging techniques, magnetic resonance imaging, and multidetector computed tomography) applicable for evaluation of the size and severity of myocardial damage in patients with AMI undergoing primary PCI. Proposed therapeutic strategies to repair irreversible myocardial damage in patients treated with primary PCI are also considered, with particular focus on the value of stem cell therapy in this specific setting.