The treatment of ST-segment elevation myocardial infarction (STEMI) has advanced dramatically over the past 30 years since the introduction of reperfusion therapies, such that mechanical reperfusion with primary percutaneous coronary intervention is now the standard of care. With STEMI, as with other forms of acute coronary syndrome, stent deployment in culprit lesions is the dominant form of reperfusion in the developed world and is supported by contemporary guidelines. However, the precise timing of stenting and the extent to which both culprit and non-culprit lesions should be treated continue to be active areas of study. In this review, we revisit key data that support the use of mechanical reperfusion therapy in STEMI patients and explore the optimal timing for and extent of stent implantation in this complex patient group. We also review data surrounding the deleterious effects of untreated residual myocardial ischemia, the importance of complete revascularization, and the recent data exploring culprit-only versus multivessel stenting in the STEMI setting.