Multivessel disease is observed in approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Data from randomized clinical trials has shown that complete revascularization in the STEMI setting improves clinical outcomes by reducing the risk of reinfarction and urgent revascularization. However, the timing and modality of revascularization of non-culprit lesions are still debated. PCI of non-culprit lesions can be performed during the index primary PCI or as a staged procedure and can be guided by angiography, functional assessment, or intracoronary imaging. In this review, we summarize the available evidence about the management of non-culprit lesions in STEMI patients with or without cardiogenic shock.