The AFFIRM study showed no clear survival advantage for a rhythm versus rate control strategy in patients with atrial fibrillation (AF). However, rhythm control with antiarrhythmic drugs (AADs) is appropriate in a large number of patients with AF. The American College of Cardiology/ American Heart Association/European Society of Cardiology AF management guidelines include a safety-based algorithm for selection of AAD therapy. Class 1C agents are recommended as first-line therapy in patients without or with minimal structural heart disease. However, market research and clinical study data indicate a growing use of class III agents (mainly amiodarone) despite long-term safety and tolerability concerns, suggesting that clinical practice does not adhere to current guidelines.