Percutaneous transluminal coronary intervention (PCI) is the most used myocardial revascularization technique for patients with coronary artery disease. Primary PCI with stent implantation is widely considered the gold standard for the treatment of ST-elevation myocardial infarction patients. Coronary stents, compared with balloon angioplasty, have reduced focal lesion restenosis. To reduce in-stent restenosis, drug-eluting stents (DES) were designed to locally release drugs inhibiting neointimal growth. Recent concerns have emerged on the potential higher risk of stent thrombosis with DES that might be even more pronounced among myocardial infarction patients. For these reasons, DES for primary PCI remains an "off-label" use. In the last several years, a number of randomized trials and registries have tested the safety and efficacy of DES in primary PCI. Data from these studies were analyzed in several meta-analyses, reasonably consistently demonstrating that the use of DES significantly decreased the need for revascularization without an increase in the incidence of death, recurrent infarction, or stent thrombosis at long-term follow-up.