Chest pain syndromes are diverse and often enigmatic. Most chest pain is of a benign nature and poses no serious threat to life. However, when presented with the patient complaining of acute chest pain, the clinician must make decisions concerning management of potentially lethal disease while considering the emotional and financial implications of overtreatment of less serious disorders. In general, life-threatening chest pain syndromes involve some form of vascular compromise (myocardial ischemia, aortic stenosis, dissection of the aorta, pulmonary embolus), and particular emphasis must be placed on detecting these entities. We have reviewed the major causes of chest pain with a perspective on newer methods for distinguishing these entities. The skilled clinician will apply this information in a judicious, systematic manner to afford the most prudent management of the patient.