There are many reasons why one might wish to suppress atrial fibrillation (AFib) and attempt to maintain sinus rhythm. This article assumes that the clinical decision to maintain sinus rhythm has been made. That being the case, antiarrhythmic drug therapy is generally the first line of treatment of AFib. Currently in the United States, there are 8 available antiarrhythmic drugs that have demonstrated efficacy for preventing AFib. The drugs are quinidine, procainamide, disopyramide, flecainide, propafenone, moricizine, sotalol, and amiodarone. Because AFib tends to recur regardless of the drug selected, recurring in at least one-half of the patients being treated, no drug is clearly better than any other for suppression of AFib. Furthermore, because AFib is rarely life-threatening, occasional recurrence should be anticipated and should not be considered failure per se. The measure of drug efficacy is the frequency of recurrence. Before initiating drug therapy, the presence or absence of structural heart disease must be determined, because in the absence of structural heart disease, antiarrhythmic drugs generally can be given rather safely, but in the presence of structural heart disease, especially when associated with ventricular dysfunction, there is an important risk of developing ventricular proarrhythmia. Considerations for specific drug selection are discussed and an algorithm for therapy is suggested.