Improving the clinical outcomes of stroke patients depends on the adoption of proven new therapies throughout the broader medical community. Approximately 1% of stroke patients in community settings are receiving tissue plasminogen activator (tPA) therapy 12 years after US Food and Drug Administration approval. Knowledge translation, the process by which the results of clinical investigations are adopted by clinicians and incorporated into routine practice, is important but often overlooked. This article reviews the history of tPA use in stroke as a case study of a breakdown of knowledge translation in emergency medicine. It reviews knowledge translation concepts and theory and explores practical community-academic collaborative methods based on these tenets to enhance acute stroke care delivery in the community setting.