Perioperative atrial fibrillation (AF) is one of the most frequent complications of cardiac surgery. Its development is associated with an increased morbidity and mortality, for example from perioperative stroke, as well as ventricular arrhythmias, postoperative myocardial infarction, congestive cardiac failure, renal failure, increased use of inotropic medications and the need for intra-aortic balloon pump. Furthermore, AF after cardiac surgery results in prolonged hospitalization after the procedure, as well as an excess utilization of hospital resources and increased hospital costs. Given the importance of AF for patient outcome, a wide variety of prophylactic pharmacologic strategies have been evaluated. The risk of post-operative AF should be reduced by the administration of amiodarone, a beta-blocker, sotalol or rate-limiting calcium antagonists. In addition, in patients undergoing cardiac surgery on pre-existing beta-blocker therapy, this treatment should be continued unless contraindications develop (such as post-operative bradycardia or hypotension). Unless contraindicated, a rhythm control strategy is recommended as the initial option for the treatment of post-operative AF following cardiothoracic surgery. More recently, some data regarding magnesium, statins and n-3 polyunsaturated fatty acids in reducing post-op AF are available. Clearly, perspectives are changing in our management of this common arrhythmia.