Abstract: Acute ST-segment elevation myocardial Infarction (STEMI) is a severe cardiovascular disease with a rapidly increasing morbidity, and often causes adverse outcomes. About 40-65% of patients presenting with STEMI have multi-vessel disease (MVD). Compared with patients with single-vessel disease, the incidence of cardiovascular events in STEMI patients with MVD is much higher. Currently, there are three strategies for the treatment of STEMI patients with MVD when coronary artery bypass grafting is not preferred: percutaneous coronary intervention (PCI) confined to culprit vessel lesions only (culprit-PCI); PCI in which lesions in the culprit vessel as well as≥1 non-infarct-related artery (nonculprit vessel lesion) are treated in the same procedure (MV-PCI); and PCI confined to culprit vessel lesions only, after which ≥1 lesions in nonculprit vessel are treated during planned secondary procedures (staged-PCI). As the pathophysiological status of the STEMI patients with MVD is relatively unique, optimal strategy of the non-infarct-related artery in STEMI patients remains unclear. With the development of advanced techniques and new oral drugs, the treatment of STEMI patients has also been improved. This article reviews the advances of strategies for the treatment of STEMI patients with MVD.