Postoperative atrial fibrillation (POAF), a common complication of cardiac surgery, can increase the morbidity and mortality, as well as the costs of the surgery being preformed. Guidelines recommend the use of β-blockers, amiodarone, or sotalol to decrease the risk of experiencing POAF. However, none of these agents fully protect the patient from POAF, thus newer agents are needed to be used in combination with them. Many different agents have been studied to fit this role and may be grouped into 2 categories: agents with antiarrhythmic activity such as magnesium and polyunsaturated fatty acids and agents with anti-inflammatory activity such as statins and free radical scavengers. Most of these novel agents have been studied in a wide variety of trials; however, some clearly have more effect than others. Although none of these newer agents have the data required to make blanket recommendations for use at this point, given the safety profile and low costs of some, many continue to be evaluated in randomized-controlled trials.