Atrial flutter is an important arrhythmia in clinical practice. Although the reentrant circuit of human typical atrial flutter is well characterized, the action of antiarrhythmic drugs on this tachycardia is less understood. Based on the recent clinical trials, pure Class III drugs like ibutilide or dofetilide are more effective in acute termination of human atrial flutter than Class I drugs like procainamide or flecainide. The mechanisms of drug induced termination of atrial flutter include refractory block due to cycle length oscillation, fixed block due to a reduced safety factor for conduction, or a collision of opposing wavefronts due to loss of the lateral boundaries or return reexcitation. Because ventricular proarrhythmia is a major concern with ibutilide or dofetilide therapy, development of new drugs with more specific target profiles is a future direction for treatment of human atrial flutter.