Although amiodarone is the most effective antiarrhythmic agent for maintaining sinus rhythm in patients with atrial fibrillation, it is generally used as the drug of the last resort in the United States. This is because long-term amiodarone therapy can potentially cause serious noncardiac side effects, such as pulmonary fibrosis, thyroid dysfunction, hepatitis, and neurotoxicity. Furthermore, it may also cause adverse interaction with digoxin, coumadin, and other antiarrhythmic drugs. Atrial fibrillation is frequently associated with a variety of cardiac disease, and its triggering factors vary among patients. Treatment strategy should be tailored to each individual patient according to the clinical presentation, concomitant disease, left ventricular function, and response (efficacy and side effects) to each drug regimen.