The extensive use of short-term oxygen therapy in acute coronary syndrome (ACS), with rarely reported adverse effects and frequent cases of anecdotal benefit, supports oxygen administration as benign intervention for cardiac patients with pain and subnormal peripheral pulse oximetry. The pain of ACS is effectively decreased by beta-blockers. Though their exact analgesia mechanism is not known, there are several possible routes by which beta-blockers could reduce pain. Nitrates dilate the epicardial coronary arteries, their collaterals, and peripheral vessels, thus improving coronary perfusion and potentiating a favorable ratio of subendocardial-to-epicardial flow. Opioids have long been a part of the ACS treatment armamentarium. Due to its properties as a pulmonary venodilator and anxiolytic, morphine has been the analgesic of choice for ACS pain. Intravenous benzodiazepines should be used for patients with cocaine-associated cardiac chest pain. In this population, the risk of vasospasm from beta-blockers is such that these agents should be avoided.