Background: Clinical trials are the foundation underlying clinical decision-making. However, stringent inclusion and exclusion criteria may reduce the generalizability of their results, especially for patients seen in the emergency department (ED). Guideline recommendations, based on clinical trials and pertinent registries, apply to broad populations, but not all patients cared for at the bedside fit the predefined categories that make guidelines practical. Furthermore, these documents may not incorporate the latest evidence. As a result, other factors (eg, individual patient characteristics, clinician experience, cost, regulatory labels, expert opinions) often result in clinical decision-making that varies from strict adherence to guideline recommendations. Objectives: These challenges demonstrate a need to integrate clinical data and guidelines advice with actual ED practice in a manner that will be consistent with decisions made later in the continuum of care. Discussion: In recognition of these issues, a roundtable was convened in New York City on June 5, 2009, to discuss the implications of recent trials involving patients with non-ST-segment elevation acute coronary syndromes. Eight physicians, representing both emergency medicine and cardiology, shared information on advances and clinical trial results in antiplatelet treatment, guidelines, and other developments in patient care. This article is based on transcripts of their presentations and the ensuing discussions that were of particular importance for emergency physicians. Conclusions: Although guidelines and clinical registries can provide broad direction for practice, there is no substitute for a prospective, multidisciplinary, institution-specific, consistent, evidence-based approach to patient management.