Chest pain presents a diagnostic challenge in outpatient family medicine. Noncardiac causes are common, but it is important not to overlook serious conditions such as an acute coronary syndrome, pulmonary embolism, or pneumonia. In addition to a thorough history and physical examination, most patients should have a chest radiograph and an electrocardiogram. Patients with chest pain that is predictably exertional, with electrocardiogram abnormalities, or with cardiac risk factors should be evaluated further with measurement of troponin levels and cardiac stress testing. Risk of pulmonary embolism can be determined with a simple prediction rule, and a D-dimer assay can help determine whether further evaluation with helical computed tomography or venous ultrasound is needed. Fever, egophony, and dullness to percussion suggest pneumonia, which can be confirmed with chest radiograph. Although some patients with chest pain have heart failure, this is unlikely in the absence of dyspnea; a brain natriuretic peptide level measurement can clarify the diagnosis. Pain reproducible by palpation is more likely to be musculoskeletal than ischemic. Chest pain also may be associated with panic disorder, for which patients can be screened with a two-item questionnaire. Clinical prediction rules can help clarify many of these diagnoses.