Approximately 1% of primary care office visits are for chest pain, and 2% to 4% of these patients will have unstable angina or myocardial infarction. Initial evaluation is based on determining whether the patient needs to be referred to a higher level of care to rule out acute coronary syndrome (ACS). A combination of age, sex, and type of chest pain can predict the likelihood of coronary artery disease as the cause of chest pain. The Marburg Heart Score and the INTERCHEST clinical decision rule can also help estimate ACS risk. Twelve-lead electrocardiography is recommended to look for ST segment changes, new-onset left bundle branch block, presence of Q waves, and new T-wave inversions. Patients with suspicion of ACS or changes on electrocardiography should be transported immediately to the emergency department. Those at low or intermediate risk of ACS can undergo exercise stress testing, coronary computed tomography angiography, or cardiac magnetic resonance imaging. In those with low suspicion for ACS, consider other diagnoses such as chest wall pain or costochondritis, gastroesophageal reflux disease, and panic disorder or anxiety states. Other less common, but important, diagnostic considerations include acute pericarditis, pneumonia, heart failure, pulmonary embolism, and acute thoracic aortic dissection.