Thrombolytic therapy remains the most commonly administered revascularization strategy for patients with ST-elevation myocardial infarctions (STEMI). However, many patients fail to have patent arteries or ST-segment resolution after these therapies. Multiple strategies have been examined to treat these patients with "failed thrombolysis." We examined the existing medical literature regarding treatment of failed thrombolysis including strategies testing repeat thrombolytic therapy and rescue percutaneous coronary intervention. Additional, we reviewed the literature regarding the efficacy of transferring patient for rescue percutaneous intervention and coronary stenting. The impact of contemporary antiplatelet strategies, cardiogenic shock, and coronary bypass surgery was examined. Overall, the management of patients with acute STEMI in whom thrombolytic therapy failed remains a challenging problem. As a result, many different strategies are currently in use. Among these therapeutic interventions, rescue PCI with coronary stenting appears to be superior when it is done in a timely manner by an experienced center.