Chest pain is the initial symptom of many life-threatening disease processes. Pain may arise from any structure located in the thoracic cavity. Cardiac causes of chest pain usually have anginal symptoms. Noncardiac causes have a variety of chest pain characteristics. Diseases that require immediate attention and intervention are myocardial infarction/unstable angina, dissecting aortic aneurysm, pericarditis, pulmonary embolism, pneumothorax, pneumonia, and acute chest syndrome. In order to evaluate a patient with the complaint of chest pain, the advanced practice nurse must be familiar with the differential diagnosis approach to acute chest pain.