This briefing paper discusses the evidence base for the development of regional systems of care for patients presenting with ST-segment elevation myocardial infarction (STEMI) and can serve as a tool for State Flex Programs in the development of these local and regional systems of care. Special emphasis is given to the role of Critical Access Hospitals (CAHs) and Emergency Medical Services (EMS) providers. This work is part of a series of Flex Monitoring Team briefs whose purpose is to identify and assess evidence-based interventions for use by State Flex Programs, CAHs, and EMS units. This briefing paper describes the evidence supporting the development of regional systems of STEMI care and includes examples that include CAHs, other rural hospitals, and rural EMS agencies. As these initiatives have both a quality improvement and a systems development focus, they provide a valuable opportunity for State Flex Programs to engage CAHs and EMS agencies in rationalizing and improving the delivery of STEMI care to rural residents.This paper discusses the vital role that rural EMS agencies and CAHs can play in regional systems of STEMI care and highlights the work of four State Flex Programs in this area. It provides a resource to State Flex Programs interested in developing interventions to engage rural EMS agencies, CAHs, and other rural and urban hospitals in developing regional systems of care.