Chest pain is one of the most frequently seen chief complaints in patients presenting to emergency departments, and is considered to be a "high-risk" chief complaint. The differential diagnosis for chest pain is broad, and potential causes range from the benign to the immediately life-threatening. Although many (if not most) emergency department patients with chest pain do not have an immediately life-threatening condition, correct diagnoses can be difficult to make, incorrect diagnoses may lead to catastrophic therapies, and failure to make a timely diagnosis may contribute to significant morbidity and mortality. Several atraumatic "high-risk" causes of chest pain are discussed in this article, including myocardial infarction and ischemia, thoracic aortic dissection, and pulmonary embolism. Also included are brief discussions of tension pneumothorax, esophageal perforation, and cardiac tamponade.