There are no perfect tests or algorithms to exclude ACI. Because acute coronary occlusion often occurs in patients with low-grade coronary stenosis, the diagnostic goal of a chest pain diagnostic protocol is not to identify patients with CAD, but rather to identify patients who may be safely discharged home without the development of complications such as MI, unstable angina, death, shock, or CHF over the next 1 to 6 months. There is an advantage to evaluating patients at the time of their symptoms. Patients who have a small plaque that is ruptured, leading to intracoronary thrombosis and ischemia, will manifest ischemia on diagnostic testing that could missed in routine outpatient testing when their plaque were stable. The diagnosis and risk stratification of acute coronary ischemia in the ED depends on a careful history and interpretation of the ECG. Multiple regression models using readily available data (e.g., history, physical examination, and ECG) provide the best tools for risk stratification. If one is deciding how to select patients for an EDOU chest pain evaluation, diagnostic tools that have previously been tested and validated in this setting are preferable. These include the Multicenter Chest Pain Study derived tools (i.e., Goldman, Lee), the ACI and ACI-TIPI tools, and sestamibi risk stratification tools. This is not to say that other tools may not play a role at individual institutions. It is probably better to select a consistent approach and evaluate its performance, rather than to allow random variation to dictate practice. The future direction probably will involve standardization of the ED chest pain population. This allows outcome and cost-effectiveness comparative research of various strategies for patients with normal or nondiagnostic ECGs and normal biomarkers. Although this approach allows more precise stratification, the risk will never be zero, meaning that there will never be a substitute for good clinical judgment and close follow-up care.