In-hospital stroke events occur less often than stroke outside of a health care facility; yet, the need for timely evaluation and treatment is the same regardless of geographic location. During hospitalization, nurses are generally the first to recognize possible symptoms of stroke and activate emergency protocols. Such actions in response to changes in patient condition are critical to optimal patient outcomes. A recent scientific statement from the American Heart Association notes that patients with in-hospital stroke are likely to experience delayed recognition of symptoms, less likely to receive intravenous thrombolysis therapy, and have worse outcomes compared with community-occurring stroke. The aim of this article is to expand upon that scientific statement to assist nurses and acute care hospitals in the United States and elsewhere with similar health care systems to create evidence-based, nurse-driven protocols for in-hospital stroke recognition and management.