The best strategy regarding percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in multivessel disease is an unresolved issue. Although current guidelines recommend that PCI in non-culprit arteries should not be attempted unless the patient is hemodynamically unstable, it is unclear whether PCI of the infarct-related artery only or a strategy of complete revascularization, either in a simultaneous or staged multivessel PCI approach, will improve outcome. Based on available data, PCI of the culprit lesion has the advantages of shorter procedure duration, a smaller amount of dye used, and a lower rate of periprocedural myocardial infarctions, while complete revascularization has lower rates of recurrent angina and a better left ventricular ejection fraction. Although data available give controversial results for the right strategy to choose, the only adequately powered randomized controlled trial shows that a strategy of multivessel PCI should be pursued notwithstanding the timing of complete revascularization. However, to avoid the potential risks of simultaneous multivessel PCI, a strategy of staged complete revascularization appears to be the best choice. It should be considered whether current guidelines should be changed to account for these considerations, and other adequately powered randomized controlled trials should be performed to endorse current knowledge.