Optimal treatment for ST-segment elevation myocardial infarction depends on early diagnosis and rapid selection of the appropriate reperfusion strategy. Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy at PCI-capable hospitals. For hospitals without PCI capability, there are 2 reperfusion strategies, primary PCI and thrombolytic therapy, which are both supported by clinical evidence and national guidelines. Transferring patients for primary PCI may cause delays and requires established, proven protocols, systems, and networks to achieve minimal door-to-balloon times. The authors review the available data and present a systematic, evidence-based approach in a simple framework to enable noncardiovascular and cardiovascular physicians to select the optimal reperfusion strategy. The framework is based on available data from clinical trials and local circumstances from clinical practice by incorporating duration of symptoms (fixed ischemia time) and anticipated transport delays to a PCI-capable facility (incurred ischemia time).