When a patient complains of chest pain, the first priority is to establish whether the situation is life threatening. Life-threatening differential diagnoses that clinicians must consider include acute coronary syndrome, cardiac tamponade, pulmonary embolus, aortic dissection, and tension pneumothorax. Nonthreatening causes of chest pain that should be considered include spontaneous pneumothorax, pleural effusion, pneumonia, valvular diseases, gastric reflux, and costochondritis. The challenge for clinicians is not to be limited by “satisfaction of search” and fail to consider important differential diagnoses. The challenge, however, can be met by developing a systematic method to assess chest pain that will lead to the appropriate diagnosis and appropriate treatment plan.