Changes in the economic and therapeutic environment have altered the time frame in which an accurate diagnosis of acute myocardial infarction (AMI) must be made. The advent of effective reperfusion therapies and the increasing emphasis on reducing cost produce an environment in which rapid diagnosis can reduce morbidity and mortality while simultaneously reducing overall cost by avoiding unnecessary hospitalization and intervention. The first element of a diagnostic strategy remains a brief, directed history and physical examination. The orientation of this phase is to identify important causes of symptoms other than AMI, while rapidly leading to more definitive evaluation for myocardial ischemia when another diagnosis is not found. The ECG provides the most rapid definitive diagnosis, but the diagnosis remains equivocal in many patients with nondiagnostic ECGs. In this group, the use of cardiac enzyme measurements early in the course holds promise in directing intensive care at high-risk patients while avoiding unnecessary intervention in low-risk patients. A protocolized approach to patient evaluation should become a part of standard practice patterns in every hospital.