Several organizations have developed guidelines for the management of ST-segment elevation myocardial infarction (STEMI). However, the optimal strategy regarding revascularization in the setting of multivessel disease, specifically with regards to culprit vessel versus complete revascularization, continues to evolve. While previous observational studies promoted culprit vessel-only intervention in patients with STEMI, recent randomized controlled trials suggest potential benefits with multivessel revascularization, either at the time of the index event or in a staged fashion, in patients without cardiogenic shock. This may be due to the known instability of non-culprit lesions in the setting of acute coronary syndrome, and the diffuse coronary processes involved. As additional literature examines culprit vessel versus multivessel revascularization strategies, clinicians continue to be tasked with determining optimal treatment plans for their patients and understanding the factors that promote selected revascularization strategies. This review summarizes and discusses observational studies, randomized control trials and current guidelines in order to evaluate optimal reperfusion strategies for patients presenting with STEMI in the setting of multivessel disease.