From the beginning of the pivotal NINDS rtPA Stroke Study in January of 1991, the past 2 decades has witnessed an incredible paradigm change in the perception and management of acute ischemic stroke. From a disease previously associated with nihilism and fatalism to one of empowerment, from both a patient and healthcare provider, stroke care in 2013 represents a revolutionary change. The early years of this revolution in care centered around new therapies and better overall acute stroke management. Later, armed with IV rt-PA and intra-arterial approaches, stroke care improved not based on new interventions but through better integration and organization of stroke resources. The coming decade will continue to see stroke care improve, largely based on these stroke systems of care. Organization of stroke care begins in the hospital, centered on the stroke team, but to truly utilize regional stroke resources, stroke systems of care must be organized within discrete regions of care to optimally educate, identify, triage, and manage all potential stroke patients. National standards for defining stroke center capabilities began in 2000. Further accreditation efforts, largely by the Joint Commission, began in 2005 and now serve as discrete measurements for stroke capabilities. Mirroring trauma system models, national organizations, such as the American Heart Association, have established best practices for acute stroke care, and defined the various capabilities of stroke hospitals at each level of capacity. Adding contemporary guidelines, again largely developed by the AHA, these guiding principles and best practices are used within regions to define best stroke practice. The 50,000 ft view of stroke systems of care focuses on the state-based systems. Within the U.S. state-based stroke systems of care provide the largest scale of stroke organization, in part because of state-based prehospital EMS organization. Even at the state level, a one size fits all approach is too broad to be effectively implemented across the various practice settings within a state. It is more effective to take national best practice and guidelines and work with state committees consisting of all the major stakeholders within a state and often lead in part by the state department of health, to translate best practice into regionally appropriate systems of care. Incorporating prehospital care into these regional plans is critical to ensure appropriate triage based on regional hospital stroke capabilities. Using nationally identified best practice with state-based guidance and organization stroke systems of care are implement within a distinct geographic region. These regions are based in part by the capabilities within a geographic region (or lack there of), and the organization and availability of prehospital care services, both Emergency Medical Services, 911 dispatch centers, and air medical services. For the complete spectrum of stroke care, rehabilitation facilities must also be considered but are typically not included in the acute phase of stroke system planning. Healthcare and patient stakeholders in these distinct regions need to meet and organize the most locally appropriate stroke system of care, and in particular, develop prehospital triage protocols of stroke patients to the most appropriate stroke hospital. Distance to various hospitals, hospital capabilities, patient preferences, and specific patient characteristics need to be considered in triage protocols but a triage process must also be simple enough to be implemented consistently in a 24/7/365 fashion to avoid prehospital confusion. Hospital-based stroke systems of care have been developed over the past several decades and with newer models of in-hospital organization built around process engineering have shown distinct improvements in time metrics and numbers of patients treated with IV rtPA. Like regional systems of care, a major driving force of internal organization is minimizing times to reperfusion inpatients that may be appropriate for these various therapies. Lastly, the success and impact of hospital, regional, and state-based stroke systems need to be evaluated on a continuing basis. Education, feedback, and refining of stroke systems of care must be in place given the changing face of healthcare and capabilities, demographic changes, and knowledge updates. When all systems work synergistically, patient outcomes can be optimized.